极速11选5

DONGWUYANJIUSUOHEZUOFAXIANXIUFUJIYINYINJIYICHANGDAFUTIGAODONGWUKELONGXIAOLV

极速11选5  TIXIBAOHEYIZHI(Somatic Cell Nuclear Transfer,SCNT)SHIZHITONGGUOXIANWEICAOZUO,JIANGDANGETIXIBAODEXIBAOHEYIZHIDAOQUHEDELUANMUXIBAOZHONGDEJISHUGUOCHENG。LUANMUXIBAODEXIBAOZHINENGJIANGTIXIBAOHEZHUANBIANWEI “QUANNENGZHUANGTAI”,BINGFAYUCHENGWEIWANZHENGDEDONGWU。XILAWEN“Klone”ZHIDESHITONGGUOQIANCHAZHITIAOLAIDUIZHIWUWUXINGFANZHIDEFANGFA。YOUYUYUQIANCHAFANZHIYOULEISIXING,TIXIBAOHEYIZHIYEBEICHENGWEIDONGWUKELONG(Cloning)。

  扦插到土壤中的枝条能否生根,是它是否能够成长为扦插植物的关键步骤。对于克隆胚胎来说,“生根”意味着在代孕母体的子宫内着床,进而形成有功能的胎盘。2006年,动物研究所周琪课题组合作发现,尽管小鼠克隆胚胎的着床前发育率可达相当水平,但其移植后的“生根”过程,即着床后的发育存在显著的异常,而这些异常主要体现在胚外组织(Extraembryonic tissues,主要形成胎盘)的发育异常1极速11选5。受限于研究手段,当时难以对克隆胎盘缺陷的本质做进一步阐释。

  2017年,利用人工构建的孤雌和孤雄胚胎和早期胚胎测序技术,哈佛大学张毅实验室发现了H3K27me3控制的印记(亲本特异性单等位表达)蛋白编码基因,其中四个(Sfmbt2,Gab1,Smoc1,Jade1)在胎盘中受H3K27me3印记,在胎儿中不印记(双等位表达)2。核移植重编程无法修正印记的缺陷。例如,对原始生殖细胞(不具备完整印记)进行克隆,无法获得具备完整印记的胚胎,也无法得到动物。一般认为,只有“印记正常”的供体细胞才能够被成功克隆。与很多情况下一样,对基础知识的更新挑战了“一般认知”:既然体细胞没有H3K27me3印记,也许所有的克隆胎盘都是“印记异常”的?这些异常对克隆胎盘的缺陷有什么贡献?

极速11选5  ZAIBENYANJIUZHONG,YANJIUTUANDUIJIANDINGLEKELONGPEITAIDEH3K27me3YINJIJIYINBIAODAQINGKUANG。HEYUQIYIZHI,ZHEIXIEJIYINZAIKELONGTAIPANZHONGCUNZAIGUODUBIAODA。YAOJINYIBUZHENGSHIZHEIZHONGGUODUBIAODADUIKELONGQUEXIANDEZUOYONG,ZEXUYAOZAIGONGTIXIBAOZHONGDANDENGWEIQIAOCHUSIGEH3K27me3YINJIJIYIN。LIYONGCHUANTONGSHOUDUANWUFAZAIXIBAOZHONGYICIXINGSHIXIANSIGEJIYINDEDANDENGWEIQIAOCHU,YINCIYANJIURENYUANLIYONGXIAOSHUDANBEITIGANXIBAOZUOWEIQIAOCHUZAITI,LIYONGJIYINBIANJIJISHUCHENGGONGHUODELEXIEDAISIGEH3K27me3YINJIJIYINDANDENGWEIQIAOCHUDETIXIBAO:PEITAICHENGXIANWEIXIBAO。JIEGUOXIANSHI,ZHEISIGEJIYINDEQIAOCHUJIDADETIGAOLETIXIBAOKELONGDEXIAOLV,CONG0%(YIZHI404MEIYESHENGXINGKELONGPEITAICHUSHENG0ZHI)TIGAODAOZUIGAO14.2%(YIZHI49MEISIQIAOCHUKELONGPEITAICHUSHENG7ZHI,SHIYANGONGHUODEXIEDAIH3K27me3YINJIJIYINQIAOCHUDEKELONGXIAOSHU39ZHI)。

  JINYIBUYANJIUFAXIAN,XIEDAIZHEISIGEJIYINDEQIAOCHUDESHIYANZUKELONGXIAOSHUDETIZHONGYUSHOUJINGLUANLAIYUANDEXIAOSHUYIZHI,ERDUIZHAOZUKELONGXIAOSHUDETIZHONGXIANZHUGAOYUSHOUJINGLUANLAIYUANDEXIAOSHU。TONGSHI,SHIYANZUKELONGXIAOSHUDETAIPANZHIJINGHEZHONGLIANGYEXIANZHUDIYUDUIZHAOZUKELONGXIAOSHU,YUSHOUJINGLUANLAIYUANDEXIAOSHUYIZHI。QIEPIANFENXIFAXIAN,ZHEISIGEH3K27me3YINJIJIYINQIAOCHUZHIHOU,KELONGTAIPANDEZIYANGCENGBILIXIANZHUTISHENG。ZIYANGCENGTIGONGTAIERYUMUTIZHIJIANDEWUZHIJIAOHUAN,SHITAIPAN“ZHAGEN”ZAIZIGONGZHONGDEZHONGYAOZUCHENGBUFEN,YESHIPEITAIZHENGCHANGFAYUDEJICHU。YESHENGXINGKELONGXIAOSHUDETAIPANJIAODA,KENENGZAIYIDINGCHENGDUSHANGBAOZHENGLEDIZIYANGCENGBILIXIAKELONGTAIERDEYINGYANGHEQITIJIAOHUAN。YISHANGJIEGUOBIAOMINGTAIPANZHONGH3K27me3YINJIJIYINYICHANG(SHUANGDENGWEIBIAODA)SHIKELONGDONGWUTAIPANYICHANGDEZHONGYAOYINSU。

  XIEDAISIGEH3K27me3YINJIJIYINDANDENGWEIQIAOCHUDEKELONGXIAOSHUKEYIZHENGCHANGCUNHUOZHICHENGNIAN,QIEZHEIXIECHENGTIXIAOSHUDETIXIBAO(WEIJIANCHENGXIANWEIXIBAO)ZAIKELONGZHONGYEZHANXIANCHUYUPEITAICHENGXIANWEIXIBAOLEISIDEKELONGXIAOLVYUBIAOXINGDEGAISHAN。ZHEISHUOMINGH3K27me3YINJIJIYINDEDANDENGWEIQIAOCHUDUIYUKELONGDETISHENGBUSHOUGONGTIXIBAONIANLINGDEXIANZHI。TONGGUOJIANGZHEIXIECHENGTIXIAOSHUYUYESHENGXINGXIAOSHUJIAOPEIHEJIYINFENLI,DEDAOLESIZHONGXIEDAIBUTONGDANH3K27me3YINJIJIYINDANDENGWEIQIAOCHUDEXIAOSHU。JINYIBUKELONGZHEIXIETIXIBAO,FAXIANSfmbt2ZAITIGAOKELONGXIAOLV,ZENGDAZIYANGCENGBILISHANGJUYOUZUIDAGONGXIAN,ERSmoc1HUOJade1QIAOCHUYEZAIGAISHANZHECHUANGHOUFAYUSHANGYOUBUTONGCHENGDUDEGONGXIAN。

  2010年,Ogura实验室报道单等位敲除Xist能显著提高小鼠克隆效率3。实验发现,尽管Xist基因在克隆胎盘中也有过表达,但在提高成纤维细胞的克隆效率上,Xist敲除不如H3K27me3印记基因四敲除(或Sfmbt2单敲除)的效果显著。研究显示,小鼠的Xist印记同样依赖于胎盘特异的H3K27me3修饰4极速11选5,这些结果说明,异常的Xist印记可能也属于本研究所揭示的H3K27me3印记依赖的体细胞克隆障碍。本研究结果显示,胎盘的H3K27me3印记异常可能在体细胞克隆胚胎中广泛存在,是克隆胎盘过大这一常见克隆动物发育缺陷的重要贡献因素;修复胎盘中H3K27me3印记基因的表达异常能够恢复克隆小鼠的体重,支持了“克隆动物的胎儿过大,起因是克隆动物的胎盘过大”这一经典假设;找到了提高克隆效率贡献度最大的H3K27me3印记基因Sfmbt2;由于成纤维细胞是猪、牛、猴等大动物克隆中的广泛使用的供体细胞,本研究的结论可能具有广泛的应用前景。

  CIYANJIUYOUZHONGGUOKEXUEYUANDONGWUYANJIUSUO、GANXIBAOYUZAISHENGYIXUECHUANGXINYANJIUYUANYUZHONGGUOKEXUEYUANYICHUANYUFAYUSHENGWUXUEYANJIUSUODENGJIGOUHEZUOWANCHENG。ZHONGGUOKEXUEYUANDONGWUYANJIUSUO、GANXIBAOYUZAISHENGYIXUECHUANGXINYANJIUYUANZHOUQIYANJIUYUAN、LIWEIYANJIUYUANJIZHONGGUOKEXUEYUANYICHUANYUFAYUSHENGWUXUEYANJIUSUOLUFALONGYANJIUYUANWEIWENZHANGDEGONGTONGTONGXUNZUOZHE。ZHONGGUOKEXUEYUANDONGWUYANJIUSUOBOSHIHOUWANGLEYUN、LIZHIKUN、WANGLIBIN,BOSHISHENGLIUCHAO、SUNXUEHANYIJIFUYANJIUYUANFENGGUIHAIWEIBENWENDEGONGTONGDIYIZUOZHE。YANJIUSHOUKEJIBU、GUOJIAZIRANKEXUEJIJINWEI、ZHONGGUOKEXUEYUAN、BOSHIHOUJIJINDENGXIANGMUDEZIZHU。

  WENZHANGLIANJIE:

XIUFUH3K27me3YINJIYICHANGNENGTIGAOKELONGXIAOLV、GAISHANKELONGXIAOSHUHEKELONGTAIPANDEFAYUBIAOXING

  CANKAOWENXIAN:

  1 Jouneau, A. et al. Developmental abnormalities of NT mouse embryos appear early after implantation. Development 133, 1597-1607, doi:10.1242/dev.02317 (2006).

  2 Inoue, A., Jiang, L., Lu, F. L., Suzuki, T. & Zhang, Y. Maternal H3K27me3 controls DNA methylation-independent imprinting. Nature 547, 419-424, doi:10.1038/nature23262 (2017).

  3 Inoue, K. et al. Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Science 330, 496-499, doi:10.1126/science.1194174 (2010).

  4 Inoue, A., Jiang, L., Lu, F. L. & Zhang, Y. Genomic imprinting of Xist by maternal H3K27me3. Gene Dev 31, 1927-1932, doi:10.1101/gad.304113.117 (2017).

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