小柯机器人

日本京都大学Yasuhiro Takashima等研究人员合作发现，来自人类多能干细胞的下胚层调控外胚层发育。这一研究成果于2023年12月5日在线发表在国际学术期刊《自然》上。

研究人员报告了利用遗传和非遗传方法，从初始人类多能干细胞（hPSC）中生成真正的下胚层（nHyC）。众所周知，其可产生胚胎发育所必需的两个胚外组织之一。nHyC自发地与初始hPSC组装在一起，形成一个具有类似羊膜腔的三维双层结构（bilaminoid）。在有第二种胚外组织（滋养层）的额外初始hPSC衍生类似物存在的情况下，bilaminoid形成的效率从20%提高到40%，而且bilaminoid内的外胚层在滋养层分泌的IL6的作用下继续发育。

此外，研究人员还发现，bilaminoid有力地再现了前后轴的模式化以及反映前原肠运动阶段的细胞形成，这些细胞的出现可以通过遗传控DKK1/OTX2外胚层样结构域来塑造。因此，研究人员成功地模拟并揭示了两种胚外组织在外胚层建立人类胚胎发育的植入后标志时有效引导特定阶段生长和进展的机制。

据悉，最近，几项使用人类胚胎培养物和单细胞RNA-seq（scRNA-seq）分析的研究揭示了人类与小鼠之间的差异，因此有必要对人类胚胎进行研究。尽管人类胚胎学非常重要，但伦理和法律限制却限制了植入后阶段的研究。因此，最近的工作重点是利用人类干细胞开发体外自组织模型。

附：英文原文

Title: Hypoblast from human pluripotent stem cells regulates epiblast development

Author: Okubo, Takumi, Rivron, Nicolas, Kabata, Mio, Masaki, Hideki, Kishimoto, Keiko, Semi, Katsunori, Nakajima-Koyama, May, Kunitomi, Haruko, Kaswandy, Belinda, Sato, Hideyuki, Nakauchi, Hiromitsu, Woltjen, Knut, Saitou, Mitinori, Sasaki, Erika, Yamamoto, Takuya, Takashima, Yasuhiro

Issue&Volume: 2023-12-05

Abstract: Recently, several studies using cultures of human embryos together with single-cell RNA-seq (scRNA-seq) analyses have revealed differences between humans and mice, necessitating the study of human embryos 1-8. Despite the importance of human embryology, ethical and legal restrictions have limited post-implantation stage studies. Thus, recent efforts have focused on developing in vitro self-organising models using human stem cells 9-17. Here, we report genetic and non-genetic approaches to generate authentic hypoblast cells (nHyC)—known to give rise to one of the two extraembryonic tissues essential for embryonic development—from nave human pluripotent stem cells (hPSCs). Our nHyCs spontaneously assemble with nave hPSCs to form a three-dimensional bilaminar structure (bilaminoids) with a pro-amniotic-like cavity. In the presence of additional nave hPSC-derived analogues of the second extraembryonic tissue, the trophectoderm, the efficiency of bilaminoid formation increases from 20% to 40%, and the epiblast within the bilaminoids continues to develop in response to trophectoderm-secreted IL6. Furthermore, we show that bilaminoids robustly recapitulate the patterning of the anterior-posterior axis and the formation of cells reflecting the pre-gastrula stage, whose emergence can be shaped by genetically manipulating the DKK1/OTX2 hypoblast-like domain. We have thus successfully modelled and revealed the mechanisms by which the two extraembryonic tissues efficiently guide the stage-specific growth and progression of the epiblast as it establishes the post-implantation landmarks of human embryogenesis.

DOI: 10.1038/s41586-023-06871-2

Source: https://www.nature.com/articles/s41586-023-06871-2

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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