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心博天下能玩吗?·娱乐

心博天下能玩吗?

【导读】近日,心博天下能玩吗?【<】【/】【s】【p】【a】【n】【>】【<】【/】【s】【p】【a】【n】【>】【 】【 】【今】【天】【头】【条】【l】【i】【t】【e】【<】【P】【>】【 】【 】【此】【外】【,】【外】【围】【商】【场】【的】【调】【整】【压】【力】【极】【有】【也】【许】【会】【进】【一】【步】【加】【快】【上】【海】【、】【北】【京】【等】【一】【线】【城】【市】【楼】【市】【调】【整】【,】【比】【方】【曩】【昔】【两】【年】【房】【企】【上】【涨】【幅】【度】【较】【大】【的】【城】【市】【:】【姑】【苏】【、】【南】【京】【、】【厦】【门】【、】【杭】【州】【等】【等】【,】【一】【旦】【这】【些】【城】【市】【首】【要】【进】【行】【商】【场】【调】【整】【,】【也】【会】【影】【响】【到】【上】【海】【、】【北】【京】【等】【一】【线】【城】【市】【楼】【市】【的】【预】【期】【。】【从】【商】【场】【个】【案】【状】【况】【来】【看】【,】【现】【在】【现】【已】【呈】【现】【深】【圳】【奥】【宸】【资】【金】【开】【裂】【的】【疑】【问】【,】【而】【这】【并】【非】【个】【案】【,】【据】【笔】【者】【了】【解】【,】【当】【时】【房】【地】【产】【商】【场】【并】【购】【商】【洽】【暗】【潮】【汹】【涌】【,】【有】【的】【公】【司】【为】【了】【剥】【离】【不】【良】【资】【产】【,】【有】【的】【公】【司】【因】【为】【资】【金】【兑】【付】【压】【力】【加】【大】【,】【有】【的】【公】【司】【是】【为】【了】【调】【整】【商】【场】【规】【划】【。】【一】【起】【,】【值】【得】【重】【视】【的】【是】【,】【在】【本】【钱】【商】【场】【环】【境】【大】【幅】【收】【紧】【,】【出】【售】【途】【径】【回】【笼】【资】【金】【遭】【受】【方】【针】【而】【瓶】【颈】【的】【下】【半】【年】【,】【商】【场】【透】【露】【出】【的】【房】【企】【资】【金】【兑】【付】【压】【力】【越】【来】【越】【大】【,】【这】【也】【就】【意】【味】【着】【下】【半】【年】【必】【然】【变】【成】【楼】【市】【深】【度】【调】【整】【的】【期】【间】【。】【<】【/】【P】【>】

心博天下能玩吗?

20200225,心博天下能玩吗?登上热搜,20200225,【<】【/】【p】【>】【 】【 】【亿】【滋】【世】【界】【<】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【2】【0】【1】【7】【 】【年】【 】【6】【 】【月】【 】【1】【6】【 】【日】【,】【北】【京】【大】【学】【生】【命】【科】【学】【学】【院】【生】【物】【动】【态】【光】【学】【成】【像】【基】【地】【汤】【富】【酬】【课】【题】【组】【在】【《】【C】【e】【l】【l】【 】【R】【e】【s】【e】【a】【r】【c】【h】【》】【杂】【志】【在】【线】【宣】【布】【了】【题】【为】【 】【“】【S】【i】【n】【g】【l】【e】【-】【c】【e】【l】【l】【 】【m】【u】【l】【t】【i】【-】【o】【m】【i】【c】【s】【 】【s】【e】【q】【u】【e】【n】【c】【i】【n】【g】【 】【o】【f】【 】【m】【o】【u】【s】【e】【 】【e】【a】【r】【l】【y】【 】【e】【m】【b】【r】【y】【o】【s】【 】【a】【n】【d】【 】【e】【m】【b】【r】【y】【o】【n】【i】【c】【 】【s】【t】【e】【m】【 】【c】【e】【l】【l】【s】【”】【 】【的】【研】【讨】【论】【文】【。】【在】【国】【际】【上】【首】【先】【开】【展】【了】【对】【一】【个】【单】【细】【胞】【一】【起】【进】【行】【染】【色】【质】【状】【况】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【、】【以】【及】【染】【色】【体】【倍】【性】【的】【全】【基】【因】【组】【测】【序】【技】【能】【(】【s】【i】【n】【g】【l】【e】【-】【c】【e】【l】【l】【 】【C】【O】【O】【L】【-】【s】【e】【q】【)】【,】【并】【选】【用】【这】【一】【技】【能】【在】【单】【细】【胞】【分】【辨】【率】【上】【体】【系】【、】【深】【化】【地】【解】【析】【了】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【表】【观】【基】【因】【组】【重】【编】【程】【的】【要】【害】【特】【征】【,】【以】【及】【染】【色】【质】【状】【况】【与】【 】【D】【N】【A】【 】【甲】【基】【化】【之】【间】【的】【互】【动】【联】【系】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【现】【有】【的】【依】【据】【高】【通】【量】【测】【序】【来】【剖】【析】【全】【基】【因】【组】【染】【色】【质】【状】【况】【的】【研】【讨】【办】【法】【通】【常】【需】【求】【很】【多】【细】【胞】【(】【例】【如】【 】【A】【T】【A】【C】【-】【s】【e】【q】【、】【D】【N】【a】【s】【e】【-】【s】【e】【q】【、】【F】【A】【I】【R】【E】【-】【s】【e】【q】【、】【M】【N】【a】【s】【e】【-】【s】【e】【q】【 】【等】【)】【。】【即】【便】【这】【些】【办】【法】【能】【够】【做】【到】【单】【细】【胞】【分】【辨】【率】【,】【也】【无】【法】【对】【同】【一】【个】【单】【细】【胞】【的】【各】【个】【表】【观】【基】【因】【组】【层】【面】【一】【起】【进】【行】【剖】【析】【,】【因】【此】【无】【法】【在】【单】【细】【胞】【分】【辨】【率】【上】【对】【多】【种】【组】【学】【之】【间】【的】【互】【动】【联】【系】【进】【行】【研】【讨】【。】【而】【汤】【富】【酬】【课】【题】【组】【将】【 】【N】【O】【M】【e】【-】【s】【e】【q】【(】【全】【基】【因】【组】【核】【小】【体】【定】【位】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【组】【测】【序】【)】【技】【能】【和】【 】【P】【B】【A】【T】【-】【s】【e】【q】【 】【技】【能】【(】【全】【基】【因】【组】【重】【亚】【硫】【酸】【盐】【测】【序】【)】【奇】【妙】【地】【联】【系】【起】【来】【(】【图】【 】【1】【)】【,】【并】【进】【行】【了】【体】【系】【的】【优】【化】【和】【进】【步】【,】【完】【结】【了】【对】【同】【一】【个】【单】【细】【胞】【进】【行】【多】【达】【 】【5】【 】【个】【层】【面】【(】【染】【色】【质】【状】【况】【、】【核】【小】【体】【定】【位】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【和】【染】【色】【体】【倍】【性】【)】【的】【基】【因】【组】【和】【表】【观】【基】【因】【组】【特】【征】【的】【剖】【析】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【1】【:】【 】【s】【i】【n】【g】【l】【e】【-】【c】【e】【l】【l】【 】【C】【O】【O】【L】【-】【s】【e】【q】【 】【原】【理】【图】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【除】【了】【能】【够】【在】【单】【细】【胞】【水】【平】【上】【一】【起】【对】【多】【种】【组】【学】【进】【行】【剖】【析】【,】【与】【现】【有】【的】【剖】【析】【染】【色】【质】【状】【况】【的】【单】【细】【胞】【测】【序】【技】【能】【比】【较】【,】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【技】【能】【还】【具】【有】【如】【下】【长】【处】【:】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【1】【)】【关】【于】【基】【因】【组】【中】【基】【地】【的】【功】【用】【元】【件】【区】【域】【具】【有】【很】【高】【的】【灵】【敏】【度】【和】【掩】【盖】【度】【。】【例】【如】【,】【关】【于】【小】【鼠】【胚】【胎】【干】【细】【胞】【系】【的】【一】【个】【单】【细】【胞】【,】【能】【够】【一】【起】【检】【查】【到】【 】【1】【8】【,】【0】【0】【0】【 】【多】【个】【基】【因】【(】【一】【切】【已】【知】【基】【因】【的】【 】【7】【5】【%】【)】【的】【发】【动】【子】【区】【域】【的】【染】【色】【质】【状】【况】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【,】【 】【也】【能】【够】【一】【起】【检】【查】【到】【 】【1】【1】【,】【0】【0】【0】【 】【多】【个】【 】【C】【p】【G】【 】【岛】【(】【一】【切】【已】【知】【 】【C】【p】【G】【 】【岛】【的】【 】【7】【0】【%】【)】【的】【染】【色】【质】【状】【况】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【;】【这】【为】【剖】【析】【干】【细】【胞】【分】【解】【发】【育】【进】【程】【中】【染】【色】【质】【状】【况】【的】【异】【质】【性】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【的】【异】【质】【性】【供】【给】【了】【强】【壮】【的】【东】【西】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【2】【)】【能】【够】【精】【准】【地】【判】【定】【出】【染】【色】【质】【的】【敞】【开】【状】【况】【和】【封】【闭】【状】【况】【,】【精】【确】【地】【把】【染】【色】【质】【封】【闭】【状】【况】【与】【因】【为】【技】【能】【因】【素】【未】【检】【查】【到】【的】【状】【况】【(】【假】【阴】【性】【)】【区】【别】【开】【来】【。】【现】【有】【的】【别】【的】【单】【细】【胞】【染】【色】【质】【状】【况】【测】【序】【技】【能】【(】【例】【如】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【和】【 】【s】【c】【D】【N】【a】【s】【e】【-】【s】【e】【q】【 】【技】【能】【)】【无】【法】【将】【染】【色】【质】【封】【闭】【状】【况】【和】【未】【检】【查】【到】【的】【状】【况】【(】【假】【阴】【性】【)】【区】【别】【开】【,】【这】【一】【缺】【点】【在】【现】【有】【技】【能】【的】【灵】【敏】【度】【比】【较】【低】【的】【状】【况】【下】【尤】【为】【严】【峻】【。】【而】【 】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【技】【能】【能】【够】【精】【确】【地】【区】【别】【染】【色】【质】【封】【闭】【状】【况】【(】【检】【查】【到】【了】【该】【基】【因】【组】【 】【D】【N】【A】【 】【片】【段】【,】【可】【是】【其】【间】【的】【 】【G】【p】【C】【 】【位】【点】【没】【有】【被】【甲】【基】【化】【)】【和】【因】【为】【技】【能】【因】【素】【未】【检】【查】【到】【的】【状】【况】【(】【没】【有】【检】【查】【到】【该】【基】【因】【组】【 】【D】【N】【A】【 】【片】【段】【)】【。】【这】【么】【对】【一】【种】【细】【胞】【类】【型】【中】【不】【一】【样】【的】【单】【个】【细】【胞】【之】【间】【同】【一】【个】【基】【因】【组】【区】【域】【的】【染】【色】【质】【敞】【开】【状】【况】【和】【封】【闭】【状】【况】【之】【间】【的】【份】【额】【能】【够】【给】【出】【精】【确】【的】【丈】【量】【成】【果】【,】【而】【不】【受】【检】【查】【灵】【敏】【度】【动】【摇】【的】【影】【响】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【3】【)】【能】【够】【对】【同】【一】【个】【 】【D】【N】【A】【 】【单】【分】【子】【一】【起】【取】【得】【其】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【信】【息】【,】【使】【得】【这】【一】【技】【能】【不】【光】【具】【有】【单】【细】【胞】【分】【辨】【率】【,】【乃】【至】【到】【达】【了】【单】【分】【子】【分】【辨】【率】【,】【能】【够】【对】【同】【一】【个】【二】【倍】【体】【细】【胞】【的】【两】【个】【等】【位】【基】【因】【别】【离】【进】【行】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【剖】【析】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【4】【)】【因】【为】【该】【办】【法】【一】【起】【扩】【增】【和】【测】【序】【敞】【开】【的】【和】【封】【闭】【的】【染】【色】【质】【区】【域】【,】【因】【此】【不】【受】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【含】【量】【动】【摇】【的】【影】【响】【。】【在】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【通】【常】【是】【环】【形】【暴】【露】【的】【 】【D】【N】【A】【,】【通】【常】【处】【于】【敞】【开】【状】【况】【。】【现】【有】【的】【别】【的】【单】【细】【胞】【染】【色】【质】【状】【况】【测】【序】【技】【能】【(】【例】【如】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【和】【 】【s】【c】【D】【N】【a】【s】【e】【-】【s】【e】【q】【 】【技】【能】【)】【因】【为】【只】【扩】【增】【和】【测】【序】【敞】【开】【的】【染】【色】【质】【区】【域】【,】【因】【此】【极】【大】【地】【受】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【含】【量】【的】【影】【响】【,】【特】【别】【是】【在】【着】【床】【前】【的】【前】【期】【胚】【胎】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【的】【含】【量】【是】【一】【般】【细】【胞】【的】【数】【十】【倍】【乃】【至】【数】【百】【倍】【,】【因】【此】【关】【于】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【和】【 】【s】【c】【D】【N】【a】【s】【e】【-】【s】【e】【q】【 】【等】【技】【能】【形】【成】【严】【峻】【影】【响】【。】【而】【 】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【技】【能】【因】【为】【一】【起】【扩】【增】【和】【测】【序】【敞】【开】【的】【和】【封】【闭】【的】【染】【色】【质】【区】【域】【而】【不】【受】【这】【一】【疑】【问】【的】【影】【响】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【5】【)】【因】【为】【掺】【入】【了】【 】【1】【0】【%】【 】【-】【 】【2】【0】【%】【 】【的】【外】【源】【 】【l】【a】【m】【b】【d】【a】【 】【D】【N】【A】【,】【所】【以】【能】【够】【精】【确】【判】【别】【所】【剖】【析】【单】【个】【细】【胞】【所】【在】【的】【细】【胞】【周】【期】【期】【间】【以】【及】【染】【色】【体】【倍】【性】【。】【这】【关】【于】【精】【确】【剖】【析】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【与】【细】【胞】【周】【期】【以】【及】【染】【色】【体】【倍】【性】【的】【联】【系】【十】【分】【有】【协】【助】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【考】【虑】【到】【多】【组】【学】【的】【信】【息】【量】【、】【有】【用】【数】【据】【量】【带】【来】【的】【昂】【扬】【测】【序】【本】【钱】【等】【疑】【问】【,】【关】【于】【细】【胞】【数】【量】【少】【,】【异】【质】【性】【强】【的】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【的】【研】【讨】【,】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【办】【法】【十】【分】【合】【适】【。】【该】【办】【法】【能】【够】【非】【常】【好】【地】【掩】【盖】【全】【基】【因】【组】【,】【有】【用】【地】【处】【理】【了】【如】【今】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【研】【讨】【中】【线】【粒】【体】【片】【段】【过】【度】【富】【集】【致】【使】【的】【有】【用】【数】【据】【量】【过】【少】【的】【疑】【问】【。】【一】【起】【,】【该】【办】【法】【能】【够】【一】【起】【剖】【析】【单】【个】【细】【胞】【中】【染】【色】【质】【敞】【开】【程】【度】【、】【核】【小】【体】【定】【位】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【、】【以】【及】【染】【色】【体】【倍】【性】【这】【 】【5】【 】【个】【组】【学】【层】【面】【,】【关】【于】【难】【以】【很】【多】【取】【得】【的】【哺】【乳】【动】【物】【前】【期】【胚】【胎】【的】【发】【育】【、】【以】【及】【杂】【乱】【的】【癌】【症】【等】【疾】【病】【研】【讨】【,】【都】【将】【供】【给】【全】【部】【有】【用】【的】【处】【理】【方】【案】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【在】【此】【根】【底】【上】【,】【该】【课】【题】【组】【运】【用】【这】【一】【新】【树】【立】【的】【 】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【办】【法】【,】【在】【单】【细】【胞】【分】【辨】【率】【体】【系】【地】【描】【写】【了】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【表】【观】【基】【因】【组】【多】【个】【层】【面】【的】【动】【态】【改】【变】【。】【高】【度】【特】【化】【的】【精】【子】【和】【卵】【细】【胞】【联】【系】【后】【,】【会】【进】【行】【一】【系】【列】【杂】【乱】【、】【精】【确】【的】【染】【色】【质】【重】【塑】【进】【程】【,】【然】【后】【树】【立】【起】【前】【期】【胚】【胎】【发】【育】【的】【全】【能】【性】【和】【多】【能】【性】【。】【对】【该】【进】【程】【的】【解】【析】【将】【有】【利】【于】【大】【家】【了】【解】【细】【胞】【多】【能】【性】【树】【立】【进】【程】【中】【的】【表】【观】【遗】【传】【调】【控】【机】【制】【以】【及】【胚】【胎】【发】【育】【反】【常】【的】【分】【子】【机】【理】【,】【该】【项】【研】【讨】【发】【现】【:】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【1】【)】【受】【精】【后】【 】【1】【2】【 】【小】【时】【以】【内】【,】【来】【自】【高】【度】【特】【化】【的】【卵】【细】【胞】【和】【精】【子】【的】【男】【女】【原】【核】【就】【阅】【历】【了】【大】【规】【模】【的】【基】【因】【组】【去】【甲】【基】【化】【,】【父】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【程】【度】【从】【精】【子】【中】【的】【 】【8】【0】【%】【(】【平】【均】【数】【)】【降】【低】【到】【雄】【原】【核】【中】【的】【 】【3】【8】【%】【(】【p】【=】【1】【.】【4】【×】【1】【0】【-】【1】【1】【)】【;】【一】【起】【母】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【程】【度】【从】【卵】【细】【胞】【中】【的】【 】【3】【2】【%】【 】【降】【低】【到】【雌】【原】【核】【中】【的】【 】【2】【8】【%】【(】【p】【=】【6】【.】【3】【×】【1】【0】【-】【5】【)】【。】【在】【此】【进】【程】【中】【,】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【体】【状】【况】【敏】【捷】【翻】【开】【,】【在】【受】【精】【卵】【的】【原】【核】【期】【就】【现】【已】【到】【达】【高】【度】【敞】【开】【的】【状】【况】【,】【随】【后】【在】【受】【精】【卵】【晚】【期】【染】【色】【质】【敞】【开】【程】【度】【大】【幅】【度】【回】【落】【,】【并】【在】【 】【2】【 】【-】【 】【细】【胞】【期】【间】【以】【后】【敞】【开】【程】【度】【再】【次】【逐】【步】【添】【加】【,】【到】【囊】【胚】【期】【时】【到】【达】【最】【高】【点】【(】【图】【 】【2】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【2】【:】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【基】【因】【组】【内】【源】【 】【D】【N】【A】【 】【甲】【基】【化】【(】【A】【)】【与】【染】【色】【质】【状】【况】【(】【B】【)】【以】【及】【染】【色】【质】【状】【况】【异】【质】【性】【(】【基】【因】【发】【动】【子】【区】【域】【;】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【o】【p】【e】【n】【、】【D】【i】【v】【e】【r】【g】【e】【n】【t】【、】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【c】【l】【o】【s】【e】【d】【 】【三】【种】【异】【质】【性】【状】【况】【)】【(】【C】【)】【(】【D】【)】【的】【动】【态】【改】【变】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【2】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【体】【系】【剖】【析】【了】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【染】【色】【质】【状】【况】【的】【异】【质】【性】【。】【依】【据】【每】【个】【基】【因】【发】【动】【子】【区】【域】【在】【同】【一】【个】【发】【育】【期】【间】【不】【一】【样】【单】【细】【胞】【之】【间】【染】【色】【质】【状】【况】【的】【异】【质】【性】【,】【将】【小】【鼠】【的】【基】【因】【划】【分】【红】【均】【匀】【敞】【开】【(】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【o】【p】【e】【n】【)】【、】【敞】【开】【 】【/】【 】【封】【闭】【混】【合】【态】【(】【D】【i】【v】【e】【r】【g】【e】【n】【t】【)】【、】【均】【匀】【封】【闭】【(】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【c】【l】【o】【s】【e】【d】【)】【这】【三】【种】【状】【况】【。】【该】【研】【讨】【发】【如】【今】【受】【精】【后】【 】【1】【2】【 】【个】【小】【时】【以】【内】【受】【精】【卵】【中】【大】【有】【些】【基】【因】【的】【发】【动】【子】【区】【域】【就】【由】【均】【匀】【封】【闭】【状】【况】【敏】【捷】【重】【编】【程】【为】【均】【匀】【敞】【开】【状】【况】【,】【为】【合】【子】【基】【因】【在】【随】【后】【的】【转】【录】【做】【好】【预】【备】【(】【图】【 】【2】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【3】【)】【经】【过】【 】【R】【N】【A】【 】【聚】【合】【酶】【按】【捺】【剂】【按】【捺】【转】【录】【的】【试】【验】【,】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【证】【实】【持】【续】【转】【录】【关】【于】【保】【持】【基】【因】【发】【动】【子】【区】【域】【的】【染】【色】【质】【敞】【开】【状】【况】【具】【有】【主】【要】【作】【用】【。】【从】【受】【精】【前】【的】【卵】【细】【胞】【到】【受】【精】【后】【的】【晚】【期】【受】【精】【卵】【期】【间】【,】【发】【动】【子】【区】【大】【片】【段】【染】【色】【质】【敞】【开】【区】【域】【(】【长】【度】【大】【于】【 】【3】【0】【0】【b】【p】【)】【的】【数】【量】【大】【幅】【度】【添】【加】【。】【该】【研】【讨】【发】【现】【,】【运】【用】【 】【R】【N】【A】【 】【聚】【合】【酶】【按】【捺】【剂】【α】【-】【A】【m】【a】【n】【i】【t】【i】【n】【 】【处】【理】【受】【精】【卵】【、】【按】【捺】【其】【转】【录】【活】【动】【,】【会】【致】【使】【数】【千】【个】【(】【5】【6】【%】【)】【基】【因】【的】【发】【动】【子】【区】【大】【片】【段】【染】【色】【质】【敞】【开】【区】【域】【从】【头】【封】【闭】【,】【阐】【明】【持】【续】【的】【转】【录】【关】【于】【保】【持】【前】【期】【胚】【胎】【中】【大】【有】【些】【基】【因】【的】【发】【动】【子】【处】【于】【敞】【开】【状】【况】【是】【必】【需】【的】【,】【染】【色】【质】【状】【况】【敞】【开】【和】【转】【录】【活】【动】【互】【相】【促】【进】【,】【一】【起】【保】【持】【合】【子】【基】【因】【的】【安】【稳】【表】【达】【(】【图】【 】【3】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【4】【)】【发】【现】【多】【能】【性】【基】【地】【因】【子】【 】【O】【c】【t】【4】【 】【的】【靶】【基】【因】【联】【系】【位】【点】【在】【 】【4】【 】【-】【 】【细】【胞】【期】【间】【就】【现】【已】【翻】【开】【并】【处】【于】【敞】【开】【状】【况】【,】【远】【早】【于】【真】【实】【树】【立】【多】【能】【性】【的】【囊】【胚】【期】【,】【暗】【示】【这】【些】【位】【点】【作】【为】【潜】【在】【的】【顺】【式】【调】【控】【元】【件】【也】【许】【参】【加】【了】【前】【期】【胚】【胎】【细】【胞】【的】【命】【运】【决】【议】【进】【程】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【5】【)】【初】【次】【在】【单】【个】【细】【胞】【内】【对】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【进】【行】【了】【深】【化】【剖】【析】【。】【从】【受】【精】【卵】【晚】【期】【到】【 】【4】【 】【细】【胞】【胚】【胎】【期】【间】【,】【在】【基】【因】【间】【区】【(】【i】【n】【t】【e】【r】【g】【e】【n】【i】【c】【 】【r】【e】【g】【i】【o】【n】【)】【父】【源】【基】【因】【组】【甲】【基】【化】【要】【显】【着】【高】【于】【母】【源】【基】【因】【组】【;】【而】【在】【基】【因】【区】【(】【g】【e】【n】【e】【 】【b】【o】【d】【y】【)】【,】【父】【源】【基】【因】【组】【甲】【基】【化】【要】【显】【着】【低】【于】【母】【源】【基】【因】【组】【。】【这】【是】【因】【为】【在】【基】【因】【间】【区】【,】【父】【源】【基】【因】【组】【的】【去】【甲】【基】【化】【速】【度】【较】【慢】【;】【而】【在】【基】【因】【区】【,】【父】【源】【基】【因】【组】【的】【去】【甲】【基】【化】【速】【度】【要】【远】【快】【于】【母】【源】【基】【因】【组】【的】【去】【甲】【基】【化】【速】【度】【。】【更】【主】【要】【的】【是】【,】【关】【于】【基】【因】【区】【,】【胚】【胎】【期】【表】【达】【水】【平】【越】【高】【的】【基】【因】【其】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【不】【对】【称】【性】【越】【激】【烈】【(】【表】【达】【水】【平】【越】【高】【,】【母】【源】【基】【因】【组】【甲】【基】【化】【就】【比】【父】【源】【基】【因】【组】【高】【越】【多】【)】【。】【与】【此】【相】【反】【,】【受】【精】【后】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【就】【敏】【捷】【同】【步】【翻】【开】【,】【到】【受】【精】【后】【 】【1】【2】【 】【小】【时】【,】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【在】【每】【个】【单】【细】【胞】【中】【就】【现】【已】【到】【达】【一】【样】【的】【敞】【开】【状】【况】【,】【并】【在】【全】【部】【植】【入】【前】【期】【间】【保】【持】【这】【一】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【之】【间】【染】【色】【质】【状】【况】【的】【精】【确】【平】【衡】【。】【这】【阐】【明】【受】【精】【后】【,】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【进】【行】【了】【不】【一】【样】【步】【的】【重】【编】【程】【进】【程】【,】【因】【为】【染】【色】【质】【状】【况】【关】【于】【合】【子】【基】【因】【的】【激】【活】【也】【许】【更】【主】【要】【,】【所】【以】【受】【精】【后】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【敏】【捷】【重】【编】【程】【、】【在】【每】【个】【单】【细】【胞】【中】【敏】【捷】【到】【达】【精】【确】【平】【衡】【并】【一】【向】【保】【持】【。】【而】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【重】【编】【程】【要】【慢】【一】【些】【并】【在】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【之】【间】【保】【持】【不】【对】【称】【散】【布】【:】【在】【基】【因】【间】【区】【,】【父】【源】【基】【因】【组】【甲】【基】【化】【高】【于】【母】【源】【基】【因】【组】【;】【而】【在】【基】【因】【区】【,】【父】【源】【基】【因】【组】【甲】【基】【化】【低】【于】【母】【源】【基】【因】【组】【,】【而】【且】【与】【胚】【胎】【期】【基】【因】【表】【达】【水】【平】【有】【关】【(】【图】【 】【4】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【4】【:】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【不】【对】【称】【散】【布】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【6】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【解】【析】【了】【雌】【性】【胚】【胎】【细】【胞】【中】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【重】【编】【程】【进】【程】【的】【异】【同】【。】【从】【配】【子】【到】【原】【核】【期】【受】【精】【卵】【,】【父】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【去】【甲】【基】【化】【速】【度】【显】【着】【比】【常】【染】【色】【体】【慢】【,】【而】【母】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【去】【甲】【基】【化】【速】【度】【和】【常】【染】【色】【体】【适】【当】【。】【从】【受】【精】【卵】【晚】【期】【到】【 】【4】【 】【细】【胞】【胚】【胎】【期】【间】【,】【父】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【显】【着】【高】【于】【母】【源】【 】【X】【 】【染】【色】【体】【,】【直】【到】【囊】【胚】【期】【,】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【才】【到】【达】【一】【起】【。】【这】【阐】【明】【受】【精】【以】【后】【,】【在】【雌】【性】【胚】【胎】【中】【失】【活】【的】【父】【源】【 】【X】【 】【染】【色】【体】【其】【 】【D】【N】【A】【 】【甲】【基】【化】【重】【编】【程】【速】【度】【要】【显】【着】【慢】【于】【活】【泼】【的】【母】【源】【 】【X】【 】【染】【色】【体】【。】【二】【者】【之】【间】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【区】【别】【一】【向】【到】【囊】【胚】【晚】【期】【才】【逐】【步】【消】【除】【。】【受】【精】【后】【,】【雌】【性】【胚】【胎】【中】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【同】【步】【进】【行】【敏】【捷】【的】【染】【色】【质】【状】【况】【重】【编】【程】【,】【并】【在】【全】【部】【植】【入】【前】【期】【间】【保】【持】【这】【一】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【之】【间】【染】【色】【质】【状】【况】【的】【精】【确】【平】【衡】【。】【(】【图】【 】【5】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【5】【:】【小】【鼠】【着】【床】【前】【雌】【性】【胚】【胎】【单】【个】【细】【胞】【中】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【的】【动】【态】【改】【变】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【7】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【提】【醒】【了】【小】【鼠】【植】【入】【前】【胚】【胎】【发】【育】【进】【程】【中】【表】【观】【基】【因】【组】【的】【异】【质】【性】【。】【受】【精】【后】【,】【基】【因】【组】【中】【大】【有】【些】【基】【因】【的】【发】【动】【子】【区】【域】【在】【同】【一】【种】【细】【胞】【的】【不】【一】【样】【单】【个】【细】【胞】【之】【间】【保】【持】【着】【均】【匀】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【均】【匀】【的】【染】【色】【质】【敞】【开】【状】【况】【。】【有】【些】【基】【因】【发】【动】【子】【区】【域】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【或】【染】【色】【质】【状】【况】【在】【同】【一】【个】【期】【间】【胚】【胎】【内】【不】【一】【样】【单】【个】【细】【胞】【之】【间】【具】【有】【激】【烈】【的】【异】【质】【性】【。】【但】【是】【,】【发】【动】【子】【区】【域】【 】【D】【N】【A】【 】【甲】【基】【化】【异】【质】【性】【激】【烈】【的】【基】【因】【和】【染】【色】【质】【状】【况】【异】【质】【性】【激】【烈】【的】【基】【因】【别】【离】【是】【两】【类】【不】【一】【样】【的】【基】【因】【。】【这】【暗】【示】【在】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【的】【进】【程】【中】【,】【染】【色】【质】【状】【况】【异】【质】【性】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【异】【质】【性】【也】【许】【别】【离】【受】【不】【一】【样】【机】【制】【的】【调】【控】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【8】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【将】【细】【胞】【周】【期】【与】【染】【色】【质】【状】【况】【联】【系】【了】【起】【来】【。】【研】【讨】【人】【员】【在】【每】【个】【单】【细】【胞】【文】【库】【中】【加】【入】【了】【等】【量】【的】【 】【l】【a】【m】【b】【d】【a】【 】【D】【N】【A】【,】【经】【过】【基】【因】【组】【测】【序】【读】【数】【和】【 】【l】【a】【m】【b】【d】【a】【 】【D】【N】【A】【 】【测】【序】【读】【数】【之】【间】【的】【份】【额】【精】【确】【推】【断】【出】【每】【个】【单】【细】【胞】【的】【倍】【性】【和】【细】【胞】【周】【期】【期】【间】【。】【该】【研】【讨】【运】【用】【小】【鼠】【胚】【胎】【干】【细】【胞】【研】【讨】【中】【已】【有】【的】【染】【色】【质】【优】【先】【仿】【制】【和】【后】【续】【仿】【制】【区】【域】【作】【为】【参】【照】【,】【发】【现】【这】【些】【区】【域】【在】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【仿】【制】【先】【后】【顺】【序】【和】【胚】【胎】【干】【细】【胞】【中】【一】【起】【,】【阐】【明】【小】【鼠】【着】【床】【前】【胚】【胎】【在】【体】【内】【发】【育】【进】【程】【中】【和】【胚】【胎】【干】【细】【胞】【运】【用】【了】【根】【本】【一】【样】【的】【一】【组】【 】【D】【N】【A】【 】【仿】【制】【开】【始】【位】【点】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【6】【:】【 】【小】【鼠】【着】【床】【前】【胚】【胎】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【重】【塑】【特】【征】【示】【意】【图】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【该】【研】【讨】【在】【国】【际】【上】【首】【先】【开】【发】【了】【对】【同】【一】【个】【单】【细】【胞】【能】【够】【一】【起】【研】【讨】【其】【染】【色】【质】【状】【况】【、】【核】【小】【体】【定】【位】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【、】【以】【及】【染】【色】【体】【倍】【性】【 】【5】【 】【个】【层】【面】【的】【单】【细】【胞】【多】【组】【学】【测】【序】【技】【能】【,】【并】【初】【次】【运】【用】【该】【技】【能】【对】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【的】【 】【7】【 】【个】【要】【害】【期】【间】【进】【行】【了】【全】【基】【因】【组】【水】【平】【、】【单】【细】【胞】【分】【辨】【率】【、】【单】【碱】【基】【精】【度】【的】【表】【观】【基】【因】【组】【研】【讨】【,】【并】【深】【度】【解】【析】【了】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【在】【着】【床】【前】【胚】【胎】【发】【育】【中】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【的】【重】【编】【程】【进】【程】【。】【该】【研】【讨】【体】【系】【地】【描】【写】【了】【高】【度】【特】【化】【的】【配】【子】【在】【受】【精】【后】【重】【编】【程】【到】【具】【有】【发】【育】【全】【能】【性】【的】【受】【精】【卵】【、】【以】【及】【进】【一】【步】【发】【育】【成】【多】【能】【性】【胚】【胎】【的】【进】【程】【中】【,】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【发】【作】【的】【精】【准】【、】【有】【序】【的】【改】【变】【,】【以】【及】【各】【个】【组】【学】【层】【面】【之】【间】【的】【互】【动】【联】【系】【(】【图】【 】【6】【)】【。】【该】【工】【作】【为】【往】【后】【大】【家】【持】【续】【研】【讨】【哺】【乳】【动】【物】【前】【期】【胚】【胎】【细】【胞】【全】【能】【性】【和】【多】【能】【性】【的】【敞】【开】【奠】【定】【了】【根】【底】【,】【一】【起】【为】【体】【细】【胞】【克】【隆】【功】【率】【的】【进】【步】【以】【及】【前】【期】【胚】【胎】【发】【育】【反】【常】【的】【确】【诊】【与】【医】【治】【供】【给】【了】【新】【思】【路】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【北】【京】【大】【学】【生】【命】【科】【学】【学】【院】【 】【B】【I】【O】【P】【I】【C】【 】【基】【地】【的】【博】【士】【后】【郭】【帆】【博】【士】【(】【现】【为】【四】【川】【大】【学】【研】【讨】【员】【)】【、】【博】【士】【生】【李】【琳】【、】【李】【静】【云】【为】【该】【论】【文】【的】【并】【列】【第】【一】【作】【者】【;】【北】【京】【大】【学】【生】【命】【科】【学】【学】【院】【汤】【富】【酬】【研】【讨】【员】【和】【四】【川】【大】【学】【郭】【帆】【研】【讨】【员】【为】【这】【篇】【文】【章】【的】【一】【起】【通】【讯】【作】【者】【。】【该】【研】【讨】【工】【作】【由】【北】【京】【大】【学】【和】【四】【川】【大】【学】【一】【起】【协】【作】【完】【结】【,】【而】【且】【得】【到】【了】【国】【家】【自】【然】【科】【学】【基】【金】【委】【员】【会】【、】【北】【京】【将】【来】【基】【因】【确】【诊】【高】【精】【尖】【立】【异】【基】【地】【,】【以】【及】【北】【大】【 】【-】【 】【清】【华】【联】【合】【基】【地】【的】【赞】【助】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【>】【<】【b】【r】【/】【>】【<】【/】【p】【>】【<】【/】【p】【>】

心博天下能玩吗?

【<】【P】【>】【我】【国】【房】【地】【产】【报】【记】【者】【了】【解】【到】【,】【2】【0】【1】【4】【年】【4】【月】【1】【7】【日】【,】【永】【升】【达】【置】【业】【有】【限】【公】【司】【将】【土】【地】【典】【当】【给】【我】【国】【长】【城】【财】【物】【处】【理】【公】【司】【海】【口】【办】【事】【处】【,】【面】【积】【为】【5】【8】【3】【4】【7】【.】【3】【8】【平】【方】【米】【,】【典】【当】【金】【额】【6】【0】【0】【0】【万】【元】【,】【典】【当】【期】【限】【为】【2】【0】【1】【4】【年】【4】【月】【1】【7】【日】【至】【2】【0】【1】【7】【年】【4】【月】【1】【7】【日】【,】【现】【在】【未】【解】【押】【。】【<】【/】【P】【>】【<】【p】【>】【<】【s】【t】【r】【o】【n】【g】【>】【 】【 】【上】【市】【缺】【乏】【三】【个】【月】【&】【n】【b】【s】【p】【;】【就】【拟】【发】【行】【优】【先】【股】【募】【资】【百】【亿】【&】【n】【b】【s】【p】【;】【<】【/】【s】【t】【r】【o】【n】【g】【>】【<】【/】【p】【>】【&】【n】【b】【s】【p】【;】【 】【&】【n】【b】【s】【p】【;】【 】【&】【n】【b】【s】【p】【;】【 】【&】【n】【b】【s】【p】【;】【 】【 】【 】【6】【月】【2】【5】【日】【,】【&】【q】【u】【o】【t】【;】【清】【华】【科】【技】【,】【荟】【萃】【同】【方】【&】【l】【d】【q】【u】【o】【;】【&】【m】【d】【a】【s】【h】【;】【&】【m】【d】【a】【s】【h】【;】【清】【华】【同】【方】【2】【0】【典】【活】【动】【在】【北】【京】【会】【议】【中】【心】【隆】【重】【召】【开】【。】【来】【自】【全】【国】【各】【地】【的】【受】【邀】【嘉】【宾】【、】【协】【作】【伙】【伴】【及】【院】【校】【领】【导】【团】【聚】【一】【堂】【,】【回】【顾】【历】【史】【,】【启】【示】【当】【下】【,】【面】【向】【未】【来】【。】

【<】【/】【p】【>】【<】【p】【>】【<】【p】【>】【当】【下】【华】【为】【在】【中】【心】【元】【器】【件】【上】【,】【具】【有】【自】【给】【自】【足】【才】【能】【的】【,】【只】【要】【麒】【麟】【处】【理】【器】【,】【经】【过】【几】【代】【的】【开】【展】【,】【华】【为】【麒】【麟】【处】【理】【器】【现】【已】【取】【得】【了】【自】【给】【自】【足】【的】【才】【能】【,】【搭】【载】【到】【了】【自】【家】【的】【智】【能】【手】【机】【上】【面】【。】【而】【依】【托】【于】【华】【为】【在】【通】【讯】【事】【务】【上】【的】【强】【势】【,】【相】【对】【而】【言】【,】【当】【下】【的】【麒】【麟】【处】【理】【器】【在】【基】【带】【方】【面】【,】【要】【强】【于】【三】【星】【的】【猎】【户】【座】【处】【理】【器】【。】【<】【/】【p】【>】

德甲

心博天下能玩吗?到底是什么情况?

【<】【p】【>】【<】【s】【t】【r】【o】【n】【g】【>】【扫】【描】【下】【方】【二】【维】【码】【,】【重】【视】【微】【信】【大】【众】【号】【&】【l】【d】【q】【u】【o】【;】【九】【正】【橱】【柜】【网】【&】【r】【d】【q】【u】【o】【;】【;】【可】【检】【查】【抢】【手】【文】【章】【《】【烟】【机】【灶】【具】【或】【再】【涨】【1】【0】【%】【~】【2】【0】【%】【,】【家】【电】【卫】【浴】【或】【再】【涨】【1】【2】【%】【~】【3】【5】【%】【,】【新】【一】【轮】【提】【价】【潮】【又】【开】【端】【了】【!】【》】【,】【想】【与】【同】【行】【沟】【通】【可】【参】【加】【橱】【柜】【沟】【通】【群】【:】【7】【4】【0】【6】【9】【8】【1】【6】【】】【<】【/】【s】【t】【r】【o】【n】【g】【>】【<】【/】【p】【>】【<】【t】【r】【>】【<】【/】【p】【>】

20200225,【<】【p】【>】【从】【基】【金】【持】【有】【人】【、】【基】【金】【申】【赎】【状】【况】【看】【,】【这】【一】【基】【金】【显】【着】【为】【委】【外】【定】【制】【基】【金】【。】【<】【/】【p】【>】【<】【p】【>】【在】【智】【能】【手】【机】【的】【全】【球】【销】【量】【上】【,】【咱】【们】【取】【两】【个】【时】【间】【段】【来】【做】【为】【衡】【量】【目】【标】【,】【一】【是】【2】【0】【1】【6】【年】【全】【年】【智】【能】【手】【机】【销】【量】【,】【二】【是】【2】【0】【1】【7】【年】【第】【一】【季】【度】【智】【能】【手】【机】【销】【量】【(】【由】【于】【第】【二】【季】【度】【的】【全】【体】【销】【量】【没】【有】【出】【炉】【)】【。】【咱】【们】【以】【业】【界】【公】【认】【比】【照】【威】【望】【的】【I】【D】【C】【数】【据】【来】【看】【一】【下】【,】【二】【者】【在】【这】【方】【面】【的】【全】【体】【体】【现】【。】【<】【/】【p】【>】【<】【p】【 】【a】【l】【i】【g】【n】【=】【"】【c】【e】【n】【t】【e】【r】【"】【>】【<】【i】【m】【g】【 】【a】【l】【t】【=】【"】【米】【家】【激】【光】【投】【影】【电】【视】【正】【式】【发】【布】【:】【1】【5】【0】【英】【寸】【/】【比】【美】【影】【院】【"】【 】【s】【r】【c】【=】【"】【/】【u】【p】【l】【o】【a】【d】【s】【/】【a】【l】【l】【i】【m】【g】【/】【1】【7】【0】【6】【2】【8】【/】【2】【0】【1】【7】【0】【6】【2】【8】【1】【6】【1】【6】【5】【7】【m】【z】【t】【2】【r】【h】【u】【y】【i】【i】【i】【1】【4】【4】【4】【.】【j】【p】【g】【"】【 】【s】【t】【y】【l】【e】【=】【"】【b】【o】【r】【d】【e】【r】【-】【b】【o】【t】【t】【o】【m】【:】【 】【b】【l】【a】【c】【k】【 】【1】【p】【x】【 】【s】【o】【l】【i】【d】【;】【 】【b】【o】【r】【d】【e】【r】【-】【l】【e】【f】【t】【:】【 】【b】【l】【a】【c】【k】【 】【1】【p】【x】【 】【s】【o】【l】【i】【d】【;】【 】【b】【o】【r】【d】【e】【r】【-】【t】【o】【p】【:】【 】【b】【l】【a】【c】【k】【 】【1】【p】【x】【 】【s】【o】【l】【i】【d】【;】【 】【b】【o】【r】【d】【e】【r】【-】【r】【i】【g】【h】【t】【:】【 】【b】【l】【a】【c】【k】【 】【1】【p】【x】【 】【s】【o】【l】【i】【d】【"】【 】【/】【>】【<】【/】【p】【>】

河南3月1日后开学

【<】【P】【>】【 】【 】【和】【讯】【房】【产】【向】【罗】【韶】【颖】【抛】【出】【一】【个】【疑】【问】【:】【将】【来】【有】【没】【有】【主】【意】【把】【原】【聚】【场】【,】【开】【展】【成】【为】【相】【似】【众】【创】【空】【间】【、】【长】【租】【公】【寓】【之】【类】【的】【房】【地】【产】【新】【业】【态】【,】【然】【后】【广】【泛】【仿】【制】【,】【成】【为】【立】【异】【的】【商】【业】【形】【式】【。】【<】【/】【P】【>】【第】【二】【是】【宅】【基】【地】【变】【革】【能】【够】【愈】【加】【灵】【敏】【。】【例】【如】【,】【将】【原】【有】【宅】【基】【地】【一】【部】【分】【复】【垦】【为】【犁】【地】【,】【犁】【地】【保】【有】【量】【添】【加】【后】【,】【再】【经】【过】【土】【地】【目】【标】【“】【增】【减】【挂】【钩】【”】【调】【剂】【,】【添】【加】【一】【部】【分】【建】【造】【用】【地】【的】【目】【标】【。】【然】【后】【使】【用】【建】【造】【用】【地】【的】【出】【让】【收】【入】【返】【还】【,】【赔】【偿】【退】【出】【宅】【基】【地】【的】【农】【人】【。】【这】【么】【既】【减】【轻】【了】【本】【地】【财】【务】【压】【力】【,】【也】【能】【保】【证】【农】【人】【利】【益】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【s】【p】【a】【n】【>】

【 】【 】【今】【天】【头】【条】【l】【i】【t】【e】【<】【P】【>】【 】【 】【此】【外】【,】【外】【围】【商】【场】【的】【调】【整】【压】【力】【极】【有】【也】【许】【会】【进】【一】【步】【加】【快】【上】【海】【、】【北】【京】【等】【一】【线】【城】【市】【楼】【市】【调】【整】【,】【比】【方】【曩】【昔】【两】【年】【房】【企】【上】【涨】【幅】【度】【较】【大】【的】【城】【市】【:】【姑】【苏】【、】【南】【京】【、】【厦】【门】【、】【杭】【州】【等】【等】【,】【一】【旦】【这】【些】【城】【市】【首】【要】【进】【行】【商】【场】【调】【整】【,】【也】【会】【影】【响】【到】【上】【海】【、】【北】【京】【等】【一】【线】【城】【市】【楼】【市】【的】【预】【期】【。】【从】【商】【场】【个】【案】【状】【况】【来】【看】【,】【现】【在】【现】【已】【呈】【现】【深】【圳】【奥】【宸】【资】【金】【开】【裂】【的】【疑】【问】【,】【而】【这】【并】【非】【个】【案】【,】【据】【笔】【者】【了】【解】【,】【当】【时】【房】【地】【产】【商】【场】【并】【购】【商】【洽】【暗】【潮】【汹】【涌】【,】【有】【的】【公】【司】【为】【了】【剥】【离】【不】【良】【资】【产】【,】【有】【的】【公】【司】【因】【为】【资】【金】【兑】【付】【压】【力】【加】【大】【,】【有】【的】【公】【司】【是】【为】【了】【调】【整】【商】【场】【规】【划】【。】【一】【起】【,】【值】【得】【重】【视】【的】【是】【,】【在】【本】【钱】【商】【场】【环】【境】【大】【幅】【收】【紧】【,】【出】【售】【途】【径】【回】【笼】【资】【金】【遭】【受】【方】【针】【而】【瓶】【颈】【的】【下】【半】【年】【,】【商】【场】【透】【露】【出】【的】【房】【企】【资】【金】【兑】【付】【压】【力】【越】【来】【越】【大】【,】【这】【也】【就】【意】【味】【着】【下】【半】【年】【必】【然】【变】【成】【楼】【市】【深】【度】【调】【整】【的】【期】【间】【。】【<】【/】【P】【>】【<】【/】【p】【>】

富易堂认证官网

【 】【 】【亿】【滋】【世】【界】【<】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【2】【0】【1】【7】【 】【年】【 】【6】【 】【月】【 】【1】【6】【 】【日】【,】【北】【京】【大】【学】【生】【命】【科】【学】【学】【院】【生】【物】【动】【态】【光】【学】【成】【像】【基】【地】【汤】【富】【酬】【课】【题】【组】【在】【《】【C】【e】【l】【l】【 】【R】【e】【s】【e】【a】【r】【c】【h】【》】【杂】【志】【在】【线】【宣】【布】【了】【题】【为】【 】【“】【S】【i】【n】【g】【l】【e】【-】【c】【e】【l】【l】【 】【m】【u】【l】【t】【i】【-】【o】【m】【i】【c】【s】【 】【s】【e】【q】【u】【e】【n】【c】【i】【n】【g】【 】【o】【f】【 】【m】【o】【u】【s】【e】【 】【e】【a】【r】【l】【y】【 】【e】【m】【b】【r】【y】【o】【s】【 】【a】【n】【d】【 】【e】【m】【b】【r】【y】【o】【n】【i】【c】【 】【s】【t】【e】【m】【 】【c】【e】【l】【l】【s】【”】【 】【的】【研】【讨】【论】【文】【。】【在】【国】【际】【上】【首】【先】【开】【展】【了】【对】【一】【个】【单】【细】【胞】【一】【起】【进】【行】【染】【色】【质】【状】【况】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【、】【以】【及】【染】【色】【体】【倍】【性】【的】【全】【基】【因】【组】【测】【序】【技】【能】【(】【s】【i】【n】【g】【l】【e】【-】【c】【e】【l】【l】【 】【C】【O】【O】【L】【-】【s】【e】【q】【)】【,】【并】【选】【用】【这】【一】【技】【能】【在】【单】【细】【胞】【分】【辨】【率】【上】【体】【系】【、】【深】【化】【地】【解】【析】【了】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【表】【观】【基】【因】【组】【重】【编】【程】【的】【要】【害】【特】【征】【,】【以】【及】【染】【色】【质】【状】【况】【与】【 】【D】【N】【A】【 】【甲】【基】【化】【之】【间】【的】【互】【动】【联】【系】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【现】【有】【的】【依】【据】【高】【通】【量】【测】【序】【来】【剖】【析】【全】【基】【因】【组】【染】【色】【质】【状】【况】【的】【研】【讨】【办】【法】【通】【常】【需】【求】【很】【多】【细】【胞】【(】【例】【如】【 】【A】【T】【A】【C】【-】【s】【e】【q】【、】【D】【N】【a】【s】【e】【-】【s】【e】【q】【、】【F】【A】【I】【R】【E】【-】【s】【e】【q】【、】【M】【N】【a】【s】【e】【-】【s】【e】【q】【 】【等】【)】【。】【即】【便】【这】【些】【办】【法】【能】【够】【做】【到】【单】【细】【胞】【分】【辨】【率】【,】【也】【无】【法】【对】【同】【一】【个】【单】【细】【胞】【的】【各】【个】【表】【观】【基】【因】【组】【层】【面】【一】【起】【进】【行】【剖】【析】【,】【因】【此】【无】【法】【在】【单】【细】【胞】【分】【辨】【率】【上】【对】【多】【种】【组】【学】【之】【间】【的】【互】【动】【联】【系】【进】【行】【研】【讨】【。】【而】【汤】【富】【酬】【课】【题】【组】【将】【 】【N】【O】【M】【e】【-】【s】【e】【q】【(】【全】【基】【因】【组】【核】【小】【体】【定】【位】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【组】【测】【序】【)】【技】【能】【和】【 】【P】【B】【A】【T】【-】【s】【e】【q】【 】【技】【能】【(】【全】【基】【因】【组】【重】【亚】【硫】【酸】【盐】【测】【序】【)】【奇】【妙】【地】【联】【系】【起】【来】【(】【图】【 】【1】【)】【,】【并】【进】【行】【了】【体】【系】【的】【优】【化】【和】【进】【步】【,】【完】【结】【了】【对】【同】【一】【个】【单】【细】【胞】【进】【行】【多】【达】【 】【5】【 】【个】【层】【面】【(】【染】【色】【质】【状】【况】【、】【核】【小】【体】【定】【位】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【和】【染】【色】【体】【倍】【性】【)】【的】【基】【因】【组】【和】【表】【观】【基】【因】【组】【特】【征】【的】【剖】【析】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【1】【:】【 】【s】【i】【n】【g】【l】【e】【-】【c】【e】【l】【l】【 】【C】【O】【O】【L】【-】【s】【e】【q】【 】【原】【理】【图】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【除】【了】【能】【够】【在】【单】【细】【胞】【水】【平】【上】【一】【起】【对】【多】【种】【组】【学】【进】【行】【剖】【析】【,】【与】【现】【有】【的】【剖】【析】【染】【色】【质】【状】【况】【的】【单】【细】【胞】【测】【序】【技】【能】【比】【较】【,】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【技】【能】【还】【具】【有】【如】【下】【长】【处】【:】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【1】【)】【关】【于】【基】【因】【组】【中】【基】【地】【的】【功】【用】【元】【件】【区】【域】【具】【有】【很】【高】【的】【灵】【敏】【度】【和】【掩】【盖】【度】【。】【例】【如】【,】【关】【于】【小】【鼠】【胚】【胎】【干】【细】【胞】【系】【的】【一】【个】【单】【细】【胞】【,】【能】【够】【一】【起】【检】【查】【到】【 】【1】【8】【,】【0】【0】【0】【 】【多】【个】【基】【因】【(】【一】【切】【已】【知】【基】【因】【的】【 】【7】【5】【%】【)】【的】【发】【动】【子】【区】【域】【的】【染】【色】【质】【状】【况】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【,】【 】【也】【能】【够】【一】【起】【检】【查】【到】【 】【1】【1】【,】【0】【0】【0】【 】【多】【个】【 】【C】【p】【G】【 】【岛】【(】【一】【切】【已】【知】【 】【C】【p】【G】【 】【岛】【的】【 】【7】【0】【%】【)】【的】【染】【色】【质】【状】【况】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【;】【这】【为】【剖】【析】【干】【细】【胞】【分】【解】【发】【育】【进】【程】【中】【染】【色】【质】【状】【况】【的】【异】【质】【性】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【的】【异】【质】【性】【供】【给】【了】【强】【壮】【的】【东】【西】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【2】【)】【能】【够】【精】【准】【地】【判】【定】【出】【染】【色】【质】【的】【敞】【开】【状】【况】【和】【封】【闭】【状】【况】【,】【精】【确】【地】【把】【染】【色】【质】【封】【闭】【状】【况】【与】【因】【为】【技】【能】【因】【素】【未】【检】【查】【到】【的】【状】【况】【(】【假】【阴】【性】【)】【区】【别】【开】【来】【。】【现】【有】【的】【别】【的】【单】【细】【胞】【染】【色】【质】【状】【况】【测】【序】【技】【能】【(】【例】【如】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【和】【 】【s】【c】【D】【N】【a】【s】【e】【-】【s】【e】【q】【 】【技】【能】【)】【无】【法】【将】【染】【色】【质】【封】【闭】【状】【况】【和】【未】【检】【查】【到】【的】【状】【况】【(】【假】【阴】【性】【)】【区】【别】【开】【,】【这】【一】【缺】【点】【在】【现】【有】【技】【能】【的】【灵】【敏】【度】【比】【较】【低】【的】【状】【况】【下】【尤】【为】【严】【峻】【。】【而】【 】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【技】【能】【能】【够】【精】【确】【地】【区】【别】【染】【色】【质】【封】【闭】【状】【况】【(】【检】【查】【到】【了】【该】【基】【因】【组】【 】【D】【N】【A】【 】【片】【段】【,】【可】【是】【其】【间】【的】【 】【G】【p】【C】【 】【位】【点】【没】【有】【被】【甲】【基】【化】【)】【和】【因】【为】【技】【能】【因】【素】【未】【检】【查】【到】【的】【状】【况】【(】【没】【有】【检】【查】【到】【该】【基】【因】【组】【 】【D】【N】【A】【 】【片】【段】【)】【。】【这】【么】【对】【一】【种】【细】【胞】【类】【型】【中】【不】【一】【样】【的】【单】【个】【细】【胞】【之】【间】【同】【一】【个】【基】【因】【组】【区】【域】【的】【染】【色】【质】【敞】【开】【状】【况】【和】【封】【闭】【状】【况】【之】【间】【的】【份】【额】【能】【够】【给】【出】【精】【确】【的】【丈】【量】【成】【果】【,】【而】【不】【受】【检】【查】【灵】【敏】【度】【动】【摇】【的】【影】【响】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【3】【)】【能】【够】【对】【同】【一】【个】【 】【D】【N】【A】【 】【单】【分】【子】【一】【起】【取】【得】【其】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【信】【息】【,】【使】【得】【这】【一】【技】【能】【不】【光】【具】【有】【单】【细】【胞】【分】【辨】【率】【,】【乃】【至】【到】【达】【了】【单】【分】【子】【分】【辨】【率】【,】【能】【够】【对】【同】【一】【个】【二】【倍】【体】【细】【胞】【的】【两】【个】【等】【位】【基】【因】【别】【离】【进】【行】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【剖】【析】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【4】【)】【因】【为】【该】【办】【法】【一】【起】【扩】【增】【和】【测】【序】【敞】【开】【的】【和】【封】【闭】【的】【染】【色】【质】【区】【域】【,】【因】【此】【不】【受】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【含】【量】【动】【摇】【的】【影】【响】【。】【在】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【通】【常】【是】【环】【形】【暴】【露】【的】【 】【D】【N】【A】【,】【通】【常】【处】【于】【敞】【开】【状】【况】【。】【现】【有】【的】【别】【的】【单】【细】【胞】【染】【色】【质】【状】【况】【测】【序】【技】【能】【(】【例】【如】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【和】【 】【s】【c】【D】【N】【a】【s】【e】【-】【s】【e】【q】【 】【技】【能】【)】【因】【为】【只】【扩】【增】【和】【测】【序】【敞】【开】【的】【染】【色】【质】【区】【域】【,】【因】【此】【极】【大】【地】【受】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【含】【量】【的】【影】【响】【,】【特】【别】【是】【在】【着】【床】【前】【的】【前】【期】【胚】【胎】【细】【胞】【中】【线】【粒】【体】【 】【D】【N】【A】【 】【的】【含】【量】【是】【一】【般】【细】【胞】【的】【数】【十】【倍】【乃】【至】【数】【百】【倍】【,】【因】【此】【关】【于】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【和】【 】【s】【c】【D】【N】【a】【s】【e】【-】【s】【e】【q】【 】【等】【技】【能】【形】【成】【严】【峻】【影】【响】【。】【而】【 】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【技】【能】【因】【为】【一】【起】【扩】【增】【和】【测】【序】【敞】【开】【的】【和】【封】【闭】【的】【染】【色】【质】【区】【域】【而】【不】【受】【这】【一】【疑】【问】【的】【影】【响】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【5】【)】【因】【为】【掺】【入】【了】【 】【1】【0】【%】【 】【-】【 】【2】【0】【%】【 】【的】【外】【源】【 】【l】【a】【m】【b】【d】【a】【 】【D】【N】【A】【,】【所】【以】【能】【够】【精】【确】【判】【别】【所】【剖】【析】【单】【个】【细】【胞】【所】【在】【的】【细】【胞】【周】【期】【期】【间】【以】【及】【染】【色】【体】【倍】【性】【。】【这】【关】【于】【精】【确】【剖】【析】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【与】【细】【胞】【周】【期】【以】【及】【染】【色】【体】【倍】【性】【的】【联】【系】【十】【分】【有】【协】【助】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【考】【虑】【到】【多】【组】【学】【的】【信】【息】【量】【、】【有】【用】【数】【据】【量】【带】【来】【的】【昂】【扬】【测】【序】【本】【钱】【等】【疑】【问】【,】【关】【于】【细】【胞】【数】【量】【少】【,】【异】【质】【性】【强】【的】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【的】【研】【讨】【,】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【办】【法】【十】【分】【合】【适】【。】【该】【办】【法】【能】【够】【非】【常】【好】【地】【掩】【盖】【全】【基】【因】【组】【,】【有】【用】【地】【处】【理】【了】【如】【今】【 】【s】【c】【A】【T】【A】【C】【-】【s】【e】【q】【 】【研】【讨】【中】【线】【粒】【体】【片】【段】【过】【度】【富】【集】【致】【使】【的】【有】【用】【数】【据】【量】【过】【少】【的】【疑】【问】【。】【一】【起】【,】【该】【办】【法】【能】【够】【一】【起】【剖】【析】【单】【个】【细】【胞】【中】【染】【色】【质】【敞】【开】【程】【度】【、】【核】【小】【体】【定】【位】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【、】【以】【及】【染】【色】【体】【倍】【性】【这】【 】【5】【 】【个】【组】【学】【层】【面】【,】【关】【于】【难】【以】【很】【多】【取】【得】【的】【哺】【乳】【动】【物】【前】【期】【胚】【胎】【的】【发】【育】【、】【以】【及】【杂】【乱】【的】【癌】【症】【等】【疾】【病】【研】【讨】【,】【都】【将】【供】【给】【全】【部】【有】【用】【的】【处】【理】【方】【案】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【在】【此】【根】【底】【上】【,】【该】【课】【题】【组】【运】【用】【这】【一】【新】【树】【立】【的】【 】【s】【c】【C】【O】【O】【L】【-】【s】【e】【q】【 】【办】【法】【,】【在】【单】【细】【胞】【分】【辨】【率】【体】【系】【地】【描】【写】【了】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【表】【观】【基】【因】【组】【多】【个】【层】【面】【的】【动】【态】【改】【变】【。】【高】【度】【特】【化】【的】【精】【子】【和】【卵】【细】【胞】【联】【系】【后】【,】【会】【进】【行】【一】【系】【列】【杂】【乱】【、】【精】【确】【的】【染】【色】【质】【重】【塑】【进】【程】【,】【然】【后】【树】【立】【起】【前】【期】【胚】【胎】【发】【育】【的】【全】【能】【性】【和】【多】【能】【性】【。】【对】【该】【进】【程】【的】【解】【析】【将】【有】【利】【于】【大】【家】【了】【解】【细】【胞】【多】【能】【性】【树】【立】【进】【程】【中】【的】【表】【观】【遗】【传】【调】【控】【机】【制】【以】【及】【胚】【胎】【发】【育】【反】【常】【的】【分】【子】【机】【理】【,】【该】【项】【研】【讨】【发】【现】【:】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【1】【)】【受】【精】【后】【 】【1】【2】【 】【小】【时】【以】【内】【,】【来】【自】【高】【度】【特】【化】【的】【卵】【细】【胞】【和】【精】【子】【的】【男】【女】【原】【核】【就】【阅】【历】【了】【大】【规】【模】【的】【基】【因】【组】【去】【甲】【基】【化】【,】【父】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【程】【度】【从】【精】【子】【中】【的】【 】【8】【0】【%】【(】【平】【均】【数】【)】【降】【低】【到】【雄】【原】【核】【中】【的】【 】【3】【8】【%】【(】【p】【=】【1】【.】【4】【×】【1】【0】【-】【1】【1】【)】【;】【一】【起】【母】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【程】【度】【从】【卵】【细】【胞】【中】【的】【 】【3】【2】【%】【 】【降】【低】【到】【雌】【原】【核】【中】【的】【 】【2】【8】【%】【(】【p】【=】【6】【.】【3】【×】【1】【0】【-】【5】【)】【。】【在】【此】【进】【程】【中】【,】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【体】【状】【况】【敏】【捷】【翻】【开】【,】【在】【受】【精】【卵】【的】【原】【核】【期】【就】【现】【已】【到】【达】【高】【度】【敞】【开】【的】【状】【况】【,】【随】【后】【在】【受】【精】【卵】【晚】【期】【染】【色】【质】【敞】【开】【程】【度】【大】【幅】【度】【回】【落】【,】【并】【在】【 】【2】【 】【-】【 】【细】【胞】【期】【间】【以】【后】【敞】【开】【程】【度】【再】【次】【逐】【步】【添】【加】【,】【到】【囊】【胚】【期】【时】【到】【达】【最】【高】【点】【(】【图】【 】【2】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【2】【:】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【基】【因】【组】【内】【源】【 】【D】【N】【A】【 】【甲】【基】【化】【(】【A】【)】【与】【染】【色】【质】【状】【况】【(】【B】【)】【以】【及】【染】【色】【质】【状】【况】【异】【质】【性】【(】【基】【因】【发】【动】【子】【区】【域】【;】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【o】【p】【e】【n】【、】【D】【i】【v】【e】【r】【g】【e】【n】【t】【、】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【c】【l】【o】【s】【e】【d】【 】【三】【种】【异】【质】【性】【状】【况】【)】【(】【C】【)】【(】【D】【)】【的】【动】【态】【改】【变】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【2】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【体】【系】【剖】【析】【了】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【染】【色】【质】【状】【况】【的】【异】【质】【性】【。】【依】【据】【每】【个】【基】【因】【发】【动】【子】【区】【域】【在】【同】【一】【个】【发】【育】【期】【间】【不】【一】【样】【单】【细】【胞】【之】【间】【染】【色】【质】【状】【况】【的】【异】【质】【性】【,】【将】【小】【鼠】【的】【基】【因】【划】【分】【红】【均】【匀】【敞】【开】【(】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【o】【p】【e】【n】【)】【、】【敞】【开】【 】【/】【 】【封】【闭】【混】【合】【态】【(】【D】【i】【v】【e】【r】【g】【e】【n】【t】【)】【、】【均】【匀】【封】【闭】【(】【H】【o】【m】【o】【g】【e】【n】【e】【o】【u】【s】【l】【y】【 】【c】【l】【o】【s】【e】【d】【)】【这】【三】【种】【状】【况】【。】【该】【研】【讨】【发】【如】【今】【受】【精】【后】【 】【1】【2】【 】【个】【小】【时】【以】【内】【受】【精】【卵】【中】【大】【有】【些】【基】【因】【的】【发】【动】【子】【区】【域】【就】【由】【均】【匀】【封】【闭】【状】【况】【敏】【捷】【重】【编】【程】【为】【均】【匀】【敞】【开】【状】【况】【,】【为】【合】【子】【基】【因】【在】【随】【后】【的】【转】【录】【做】【好】【预】【备】【(】【图】【 】【2】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【3】【)】【经】【过】【 】【R】【N】【A】【 】【聚】【合】【酶】【按】【捺】【剂】【按】【捺】【转】【录】【的】【试】【验】【,】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【证】【实】【持】【续】【转】【录】【关】【于】【保】【持】【基】【因】【发】【动】【子】【区】【域】【的】【染】【色】【质】【敞】【开】【状】【况】【具】【有】【主】【要】【作】【用】【。】【从】【受】【精】【前】【的】【卵】【细】【胞】【到】【受】【精】【后】【的】【晚】【期】【受】【精】【卵】【期】【间】【,】【发】【动】【子】【区】【大】【片】【段】【染】【色】【质】【敞】【开】【区】【域】【(】【长】【度】【大】【于】【 】【3】【0】【0】【b】【p】【)】【的】【数】【量】【大】【幅】【度】【添】【加】【。】【该】【研】【讨】【发】【现】【,】【运】【用】【 】【R】【N】【A】【 】【聚】【合】【酶】【按】【捺】【剂】【α】【-】【A】【m】【a】【n】【i】【t】【i】【n】【 】【处】【理】【受】【精】【卵】【、】【按】【捺】【其】【转】【录】【活】【动】【,】【会】【致】【使】【数】【千】【个】【(】【5】【6】【%】【)】【基】【因】【的】【发】【动】【子】【区】【大】【片】【段】【染】【色】【质】【敞】【开】【区】【域】【从】【头】【封】【闭】【,】【阐】【明】【持】【续】【的】【转】【录】【关】【于】【保】【持】【前】【期】【胚】【胎】【中】【大】【有】【些】【基】【因】【的】【发】【动】【子】【处】【于】【敞】【开】【状】【况】【是】【必】【需】【的】【,】【染】【色】【质】【状】【况】【敞】【开】【和】【转】【录】【活】【动】【互】【相】【促】【进】【,】【一】【起】【保】【持】【合】【子】【基】【因】【的】【安】【稳】【表】【达】【(】【图】【 】【3】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【4】【)】【发】【现】【多】【能】【性】【基】【地】【因】【子】【 】【O】【c】【t】【4】【 】【的】【靶】【基】【因】【联】【系】【位】【点】【在】【 】【4】【 】【-】【 】【细】【胞】【期】【间】【就】【现】【已】【翻】【开】【并】【处】【于】【敞】【开】【状】【况】【,】【远】【早】【于】【真】【实】【树】【立】【多】【能】【性】【的】【囊】【胚】【期】【,】【暗】【示】【这】【些】【位】【点】【作】【为】【潜】【在】【的】【顺】【式】【调】【控】【元】【件】【也】【许】【参】【加】【了】【前】【期】【胚】【胎】【细】【胞】【的】【命】【运】【决】【议】【进】【程】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【5】【)】【初】【次】【在】【单】【个】【细】【胞】【内】【对】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【以】【及】【 】【D】【N】【A】【 】【甲】【基】【化】【进】【行】【了】【深】【化】【剖】【析】【。】【从】【受】【精】【卵】【晚】【期】【到】【 】【4】【 】【细】【胞】【胚】【胎】【期】【间】【,】【在】【基】【因】【间】【区】【(】【i】【n】【t】【e】【r】【g】【e】【n】【i】【c】【 】【r】【e】【g】【i】【o】【n】【)】【父】【源】【基】【因】【组】【甲】【基】【化】【要】【显】【着】【高】【于】【母】【源】【基】【因】【组】【;】【而】【在】【基】【因】【区】【(】【g】【e】【n】【e】【 】【b】【o】【d】【y】【)】【,】【父】【源】【基】【因】【组】【甲】【基】【化】【要】【显】【着】【低】【于】【母】【源】【基】【因】【组】【。】【这】【是】【因】【为】【在】【基】【因】【间】【区】【,】【父】【源】【基】【因】【组】【的】【去】【甲】【基】【化】【速】【度】【较】【慢】【;】【而】【在】【基】【因】【区】【,】【父】【源】【基】【因】【组】【的】【去】【甲】【基】【化】【速】【度】【要】【远】【快】【于】【母】【源】【基】【因】【组】【的】【去】【甲】【基】【化】【速】【度】【。】【更】【主】【要】【的】【是】【,】【关】【于】【基】【因】【区】【,】【胚】【胎】【期】【表】【达】【水】【平】【越】【高】【的】【基】【因】【其】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【不】【对】【称】【性】【越】【激】【烈】【(】【表】【达】【水】【平】【越】【高】【,】【母】【源】【基】【因】【组】【甲】【基】【化】【就】【比】【父】【源】【基】【因】【组】【高】【越】【多】【)】【。】【与】【此】【相】【反】【,】【受】【精】【后】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【就】【敏】【捷】【同】【步】【翻】【开】【,】【到】【受】【精】【后】【 】【1】【2】【 】【小】【时】【,】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【在】【每】【个】【单】【细】【胞】【中】【就】【现】【已】【到】【达】【一】【样】【的】【敞】【开】【状】【况】【,】【并】【在】【全】【部】【植】【入】【前】【期】【间】【保】【持】【这】【一】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【之】【间】【染】【色】【质】【状】【况】【的】【精】【确】【平】【衡】【。】【这】【阐】【明】【受】【精】【后】【,】【染】【色】【质】【状】【况】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【进】【行】【了】【不】【一】【样】【步】【的】【重】【编】【程】【进】【程】【,】【因】【为】【染】【色】【质】【状】【况】【关】【于】【合】【子】【基】【因】【的】【激】【活】【也】【许】【更】【主】【要】【,】【所】【以】【受】【精】【后】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【的】【染】【色】【质】【状】【况】【敏】【捷】【重】【编】【程】【、】【在】【每】【个】【单】【细】【胞】【中】【敏】【捷】【到】【达】【精】【确】【平】【衡】【并】【一】【向】【保】【持】【。】【而】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【重】【编】【程】【要】【慢】【一】【些】【并】【在】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【之】【间】【保】【持】【不】【对】【称】【散】【布】【:】【在】【基】【因】【间】【区】【,】【父】【源】【基】【因】【组】【甲】【基】【化】【高】【于】【母】【源】【基】【因】【组】【;】【而】【在】【基】【因】【区】【,】【父】【源】【基】【因】【组】【甲】【基】【化】【低】【于】【母】【源】【基】【因】【组】【,】【而】【且】【与】【胚】【胎】【期】【基】【因】【表】【达】【水】【平】【有】【关】【(】【图】【 】【4】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【4】【:】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【不】【对】【称】【散】【布】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【6】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【解】【析】【了】【雌】【性】【胚】【胎】【细】【胞】【中】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【重】【编】【程】【进】【程】【的】【异】【同】【。】【从】【配】【子】【到】【原】【核】【期】【受】【精】【卵】【,】【父】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【去】【甲】【基】【化】【速】【度】【显】【着】【比】【常】【染】【色】【体】【慢】【,】【而】【母】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【去】【甲】【基】【化】【速】【度】【和】【常】【染】【色】【体】【适】【当】【。】【从】【受】【精】【卵】【晚】【期】【到】【 】【4】【 】【细】【胞】【胚】【胎】【期】【间】【,】【父】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【显】【着】【高】【于】【母】【源】【 】【X】【 】【染】【色】【体】【,】【直】【到】【囊】【胚】【期】【,】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【水】【平】【才】【到】【达】【一】【起】【。】【这】【阐】【明】【受】【精】【以】【后】【,】【在】【雌】【性】【胚】【胎】【中】【失】【活】【的】【父】【源】【 】【X】【 】【染】【色】【体】【其】【 】【D】【N】【A】【 】【甲】【基】【化】【重】【编】【程】【速】【度】【要】【显】【着】【慢】【于】【活】【泼】【的】【母】【源】【 】【X】【 】【染】【色】【体】【。】【二】【者】【之】【间】【 】【D】【N】【A】【 】【甲】【基】【化】【的】【区】【别】【一】【向】【到】【囊】【胚】【晚】【期】【才】【逐】【步】【消】【除】【。】【受】【精】【后】【,】【雌】【性】【胚】【胎】【中】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【同】【步】【进】【行】【敏】【捷】【的】【染】【色】【质】【状】【况】【重】【编】【程】【,】【并】【在】【全】【部】【植】【入】【前】【期】【间】【保】【持】【这】【一】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【之】【间】【染】【色】【质】【状】【况】【的】【精】【确】【平】【衡】【。】【(】【图】【 】【5】【)】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【5】【:】【小】【鼠】【着】【床】【前】【雌】【性】【胚】【胎】【单】【个】【细】【胞】【中】【爸】【爸】【妈】【妈】【源】【 】【X】【 】【染】【色】【体】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【的】【动】【态】【改】【变】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【7】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【提】【醒】【了】【小】【鼠】【植】【入】【前】【胚】【胎】【发】【育】【进】【程】【中】【表】【观】【基】【因】【组】【的】【异】【质】【性】【。】【受】【精】【后】【,】【基】【因】【组】【中】【大】【有】【些】【基】【因】【的】【发】【动】【子】【区】【域】【在】【同】【一】【种】【细】【胞】【的】【不】【一】【样】【单】【个】【细】【胞】【之】【间】【保】【持】【着】【均】【匀】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【均】【匀】【的】【染】【色】【质】【敞】【开】【状】【况】【。】【有】【些】【基】【因】【发】【动】【子】【区】【域】【的】【 】【D】【N】【A】【 】【甲】【基】【化】【或】【染】【色】【质】【状】【况】【在】【同】【一】【个】【期】【间】【胚】【胎】【内】【不】【一】【样】【单】【个】【细】【胞】【之】【间】【具】【有】【激】【烈】【的】【异】【质】【性】【。】【但】【是】【,】【发】【动】【子】【区】【域】【 】【D】【N】【A】【 】【甲】【基】【化】【异】【质】【性】【激】【烈】【的】【基】【因】【和】【染】【色】【质】【状】【况】【异】【质】【性】【激】【烈】【的】【基】【因】【别】【离】【是】【两】【类】【不】【一】【样】【的】【基】【因】【。】【这】【暗】【示】【在】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【的】【进】【程】【中】【,】【染】【色】【质】【状】【况】【异】【质】【性】【和】【 】【D】【N】【A】【 】【甲】【基】【化】【异】【质】【性】【也】【许】【别】【离】【受】【不】【一】【样】【机】【制】【的】【调】【控】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【(】【8】【)】【初】【次】【在】【单】【细】【胞】【分】【辨】【率】【将】【细】【胞】【周】【期】【与】【染】【色】【质】【状】【况】【联】【系】【了】【起】【来】【。】【研】【讨】【人】【员】【在】【每】【个】【单】【细】【胞】【文】【库】【中】【加】【入】【了】【等】【量】【的】【 】【l】【a】【m】【b】【d】【a】【 】【D】【N】【A】【,】【经】【过】【基】【因】【组】【测】【序】【读】【数】【和】【 】【l】【a】【m】【b】【d】【a】【 】【D】【N】【A】【 】【测】【序】【读】【数】【之】【间】【的】【份】【额】【精】【确】【推】【断】【出】【每】【个】【单】【细】【胞】【的】【倍】【性】【和】【细】【胞】【周】【期】【期】【间】【。】【该】【研】【讨】【运】【用】【小】【鼠】【胚】【胎】【干】【细】【胞】【研】【讨】【中】【已】【有】【的】【染】【色】【质】【优】【先】【仿】【制】【和】【后】【续】【仿】【制】【区】【域】【作】【为】【参】【照】【,】【发】【现】【这】【些】【区】【域】【在】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【进】【程】【中】【仿】【制】【先】【后】【顺】【序】【和】【胚】【胎】【干】【细】【胞】【中】【一】【起】【,】【阐】【明】【小】【鼠】【着】【床】【前】【胚】【胎】【在】【体】【内】【发】【育】【进】【程】【中】【和】【胚】【胎】【干】【细】【胞】【运】【用】【了】【根】【本】【一】【样】【的】【一】【组】【 】【D】【N】【A】【 】【仿】【制】【开】【始】【位】【点】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【图】【 】【6】【:】【 】【小】【鼠】【着】【床】【前】【胚】【胎】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【重】【塑】【特】【征】【示】【意】【图】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【该】【研】【讨】【在】【国】【际】【上】【首】【先】【开】【发】【了】【对】【同】【一】【个】【单】【细】【胞】【能】【够】【一】【起】【研】【讨】【其】【染】【色】【质】【状】【况】【、】【核】【小】【体】【定】【位】【、】【D】【N】【A】【 】【甲】【基】【化】【、】【基】【因】【组】【拷】【贝】【数】【变】【异】【、】【以】【及】【染】【色】【体】【倍】【性】【 】【5】【 】【个】【层】【面】【的】【单】【细】【胞】【多】【组】【学】【测】【序】【技】【能】【,】【并】【初】【次】【运】【用】【该】【技】【能】【对】【小】【鼠】【着】【床】【前】【胚】【胎】【发】【育】【的】【 】【7】【 】【个】【要】【害】【期】【间】【进】【行】【了】【全】【基】【因】【组】【水】【平】【、】【单】【细】【胞】【分】【辨】【率】【、】【单】【碱】【基】【精】【度】【的】【表】【观】【基】【因】【组】【研】【讨】【,】【并】【深】【度】【解】【析】【了】【爸】【爸】【妈】【妈】【源】【基】【因】【组】【在】【着】【床】【前】【胚】【胎】【发】【育】【中】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【的】【重】【编】【程】【进】【程】【。】【该】【研】【讨】【体】【系】【地】【描】【写】【了】【高】【度】【特】【化】【的】【配】【子】【在】【受】【精】【后】【重】【编】【程】【到】【具】【有】【发】【育】【全】【能】【性】【的】【受】【精】【卵】【、】【以】【及】【进】【一】【步】【发】【育】【成】【多】【能】【性】【胚】【胎】【的】【进】【程】【中】【,】【 】【D】【N】【A】【 】【甲】【基】【化】【和】【染】【色】【质】【状】【况】【发】【作】【的】【精】【准】【、】【有】【序】【的】【改】【变】【,】【以】【及】【各】【个】【组】【学】【层】【面】【之】【间】【的】【互】【动】【联】【系】【(】【图】【 】【6】【)】【。】【该】【工】【作】【为】【往】【后】【大】【家】【持】【续】【研】【讨】【哺】【乳】【动】【物】【前】【期】【胚】【胎】【细】【胞】【全】【能】【性】【和】【多】【能】【性】【的】【敞】【开】【奠】【定】【了】【根】【底】【,】【一】【起】【为】【体】【细】【胞】【克】【隆】【功】【率】【的】【进】【步】【以】【及】【前】【期】【胚】【胎】【发】【育】【反】【常】【的】【确】【诊】【与】【医】【治】【供】【给】【了】【新】【思】【路】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【 】【s】【t】【y】【l】【e】【=】【"】【t】【e】【x】【t】【-】【i】【n】【d】【e】【n】【t】【:】【 】【2】【e】【m】【;】【"】【>】【<】【s】【p】【a】【n】【 】【s】【t】【y】【l】【e】【=】【"】【f】【o】【n】【t】【-】【s】【i】【z】【e】【:】【 】【1】【4】【p】【x】【;】【"】【>】【北】【京】【大】【学】【生】【命】【科】【学】【学】【院】【 】【B】【I】【O】【P】【I】【C】【 】【基】【地】【的】【博】【士】【后】【郭】【帆】【博】【士】【(】【现】【为】【四】【川】【大】【学】【研】【讨】【员】【)】【、】【博】【士】【生】【李】【琳】【、】【李】【静】【云】【为】【该】【论】【文】【的】【并】【列】【第】【一】【作】【者】【;】【北】【京】【大】【学】【生】【命】【科】【学】【学】【院】【汤】【富】【酬】【研】【讨】【员】【和】【四】【川】【大】【学】【郭】【帆】【研】【讨】【员】【为】【这】【篇】【文】【章】【的】【一】【起】【通】【讯】【作】【者】【。】【该】【研】【讨】【工】【作】【由】【北】【京】【大】【学】【和】【四】【川】【大】【学】【一】【起】【协】【作】【完】【结】【,】【而】【且】【得】【到】【了】【国】【家】【自】【然】【科】【学】【基】【金】【委】【员】【会】【、】【北】【京】【将】【来】【基】【因】【确】【诊】【高】【精】【尖】【立】【异】【基】【地】【,】【以】【及】【北】【大】【 】【-】【 】【清】【华】【联】【合】【基】【地】【的】【赞】【助】【。】【<】【/】【s】【p】【a】【n】【>】【<】【/】【p】【>】【<】【p】【>】【<】【b】【r】【/】【>】【<】【/】【p】【>】【<】【/】【p】【>】【<】【P】【>】【我】【国】【房】【地】【产】【报】【记】【者】【了】【解】【到】【,】【2】【0】【1】【4】【年】【4】【月】【1】【7】【日】【,】【永】【升】【达】【置】【业】【有】【限】【公】【司】【将】【土】【地】【典】【当】【给】【我】【国】【长】【城】【财】【物】【处】【理】【公】【司】【海】【口】【办】【事】【处】【,】【面】【积】【为】【5】【8】【3】【4】【7】【.】【3】【8】【平】【方】【米】【,】【典】【当】【金】【额】【6】【0】【0】【0】【万】【元】【,】【典】【当】【期】【限】【为】【2】【0】【1】【4】【年】【4】【月】【1】【7】【日】【至】【2】【0】【1】【7】【年】【4】【月】【1】【7】【日】【,】【现】【在】【未】【解】【押】【。】【<】【/】【P】【>】

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