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完全胚胎干细胞来源的小鼠胚胎模型经历了神经元和心脏的发育过程
2022-09-11 18:14

英国剑桥大学Magdalena Zernicka-Goetz和以色列魏茨曼科学研究所Yonatan Stelzer团队共同合作近期取得重要工作进展,他们研究发现完全由胚胎干细胞来源的小鼠胚胎模型经历了神经元和心脏的发育过程。该项研究成果2022年9月8日在线发表于《细胞—干细胞》杂志上。

为了克服这一困难,研究人员开发了一种基于小鼠ESC的体外模型,该模型通过转录因子介导的诱导,重建了多能ESC谱系和植入后胚胎的两个胚外谱系。这个统一的模型再现了胚胎第5.5天到第8.5天的发育事件,包括原肠胚形成;形成前后轴、大脑和跳动的心脏结构;以及胚胎外组织的发育,包括卵黄囊和绒毛膜。将来自单个结构的单细胞RNA测序与时间匹配的天然胚胎进行比较,发现了跨谱系的非常相似的转录程序,但也显示了该模型何时何地与自然程序不同。他们的研究结果表明ESC具有较高的可塑性,可以自我组织并产生类似全胚胎样的结构。

据了解,已经建立了几个体外模型来完全利用胚胎干细胞(ESCs)再现小鼠胚胎发生的过程。尽管模仿了早期发育的许多方面,但它们未能捕捉到胚胎和胚胎外组织之间的相互作用。

附:英文原文

Title: Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development

Author: Kasey Y.C. Lau, Hernan Rubinstein, Carlos W. Gantner, Ron Hadas, Gianluca Amadei, Yonatan Stelzer, Magdalena Zernicka-Goetz

Issue&Volume: 2022-09-08

Abstract: Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure.

DOI: 10.1016/j.stem.2022.08.013

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00377-0

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:25.269
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx


本期文章:《细胞—干细胞》:Online/在线发表

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