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Nature:胚胎着床过程的体外研究

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剑桥大学的科学家们五月四日在Nature和Nature Cell Biology杂志上同时发表两篇文章,展示了他们研究人类胚胎取得的突破性成果。这两项研究不仅揭示了人类胚胎发育的关键时期,还开辟了一条提高IVF成功率的新途径。

 
人类的卵子在受精之后会分裂几次,生成一个小小的干细胞球。大约在受精第三天,这些干细胞开始聚集在胚胎一侧,形成囊胚。科学家们已经通过体外培养广泛研究了人类胚胎的着床前阶段,也就是囊胚还未在子宫着床的时期。然而人类胚胎必须在受精第七天植入子宫,只有这样胚胎才能够存活并进一步发育。
 
胚胎不能在子宫着床是早期妊娠失败的主要原因,但人们对这一阶段发生的细胞和分子改变还知之甚少。我们显然不可能仔细研究子宫内正在发育的胚胎,受精超过七天的胚胎又无法进行体外培养。剑桥大学的Magdalena Zernicka-Goetz教授基于自己此前的小鼠工作,开发了能够支持人类胚胎发育13天的体外培养体系。研究显示,只要培养条件正确,人们就可以在体外观察到着床后的人类胚胎重组。
 
“着床是人类发育的一个里程碑,从这个阶段起胚胎真正开始成形,发育计划得到确立。着床也是一个容易出现发育缺陷的妊娠阶段,”Zernicka-Goetz教授说。研究人员使用自己开发的技术密切跟踪了人类胚胎发育。他们发现,囊胚“着床”之后立刻发生细胞重组并形成空腔。这种空腔是着床后人类胚胎的基本结构,也是胚胎进一步发育的基础。
 
过去人们普遍认为这种腔是细胞凋亡形成的。但这项研究表明,人类胚胎形成空腔并不需要细胞死亡。“这一过程与我们在小鼠胚胎中观察到的现象类似,虽然小鼠和人类的着床后胚胎在结构上存在显著差异,”Zernicka-Goetz指出。“由此可见,囊胚的细胞重组是一个相当保守的过程。”
 
参阅文献:
Self-organization of the human embryo in the absence of maternal tissues
Nature Cell Biology (2016) doi:10.1038/ncb3347, Published online 04 May 2016
 
Remodelling of the human embryo at implantation is indispensable for successful pregnancy. Yet it has remained mysterious because of the experimental hurdles that beset the study of this developmental phase. Here, we establish an in vitro system to culture human embryos through implantation stages in the absence of maternal tissues and reveal the key events of early human morphogenesis. These include segregation of the pluripotent embryonic and extra-embryonic lineages, and morphogenetic rearrangements leading to generation of a bilaminar disc, formation of a pro-amniotic cavity within the embryonic lineage, appearance of the prospective yolk sac, and trophoblast differentiation. Using human embryos and human pluripotent stem cells, we show that the reorganization of the embryonic lineage is mediated by cellular polarization leading to cavity formation. Together, our results indicate that the critical remodelling events at this stage of human development are embryo-autonomous, highlighting the remarkable and unanticipated self-organizing properties of human embryos.
 
Self-organization of the in vitro attached human embryo
Nature (2016) doi:10.1038/nature17948, Published online 04 May 2016
 
Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system1, 2 to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy.
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