近日，比利时鲁汶大学Vincent Pasque和Bradley Philip Balaton研究组合作，使用先天多能干细胞模拟人类胚外中胚层 (EXM)细胞。相关论文于2022年9月1日发表在《细胞—干细胞》杂志上。

他们发现先天人类多能干细胞(hPSCs)能够分化成EXM细胞(EXMCs)。EXMC通过抑制Nodal信号和GSK3B来指定，由mTOR和BMP4信号活性维持，它们的转录组和表观基因组与人和猴胚胎EXM的转录组和表观基因组非常相似。EXMCs是间充质的，可以来自外胚层中间体，并且能够自我更新。因此，通过植入和原肠胚形成之间的灵长类动物特异性规范产生的EXMC可以在体外建模。

他们还发现，通过三重抑制形成的人类胚泡内大多数罕见的脱靶细胞对应于EXMC。他们的研究影响了我们对早期人类胚胎发生和相关缺陷的分子机制进行建模和研究的能力。

据介绍，灵长类动物着床后胚胎发生的一个标志是原肠胚形成前EXM的规格，而啮齿动物仅在原肠胚形成后形成该组织。

附：英文原文

Title: Modeling human extraembryonic mesoderm cells using naive pluripotent stem cells

Author: Thi Xuan Ai Pham, Amitesh Panda, Harunobu Kagawa, San Kit To, Cankat Ertekin, Grigorios Georgolopoulos, Sam S.F.A. van Knippenberg, Ryan Nicolaas Allsop, Alexandre Bruneau, Jonathan Sai-Hong Chui, Lotte Vanheer, Adrian Janiszewski, Joel Chappell, Michael Oberhuemer, Raissa Songwa Tchinda, Irene Talon, Sherif Khodeer, Janet Rossant, Frederic Lluis, Laurent David, Nicolas Rivron, Bradley Philip Balaton, Vincent Pasque

Issue&Volume: 2022/09/01

Abstract: A hallmark of primate postimplantation embryogenesis is the specification of extraembryonic mesoderm (EXM) before gastrulation, in contrast to rodents where this tissue is formed only after gastrulation. Here, we discover that naive human pluripotent stem cells (hPSCs) are competent to differentiate into EXM cells (EXMCs). EXMCs are specified by inhibition of Nodal signaling and GSK3B, are maintained by mTOR and BMP4 signaling activity, and their transcriptome and epigenome closely resemble that of human and monkey embryo EXM. EXMCs are mesenchymal, can arise from an epiblast intermediate, and are capable of self-renewal. Thus, EXMCs arising via primate-specific specification between implantation and gastrulation can be modeled in vitro. We also find that most of the rare off-target cells within human blastoids formed by triple inhibition.

DOI: 10.1016/j.stem.2022.08.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00337-X