以色列魏茨曼科学研究所Yonatan Stelzer和Amos Tanay共同合作，近期取得重要工作进展。他们发现了小鼠胚胎及胚外组织发育中BMP4表达的时序性差异调控机制。相关研究成果2024年9月18日在线发表于《自然》杂志上。

据介绍，小鼠发育中的胎盘起源于胚胎外胚层（ExE），对哺乳动物胚胎发育至关重要。然而，对ExE分化动力学及其和胚胎本身相互作用的描述仍然不完整。

研究人员开发了一种小鼠原肠胚形成的时间单细胞模型，该模型描绘了胚胎和胚胎外谱系中的连续和平行分化。这与三向扰动方法相匹配，以靶向来自胚胎本身、单独的ExE或两者的信号。研究人员发现，ExE特化涉及未分化的外胎盘锥细胞和绒毛膜祖细胞的早期空间和转录差异。

绒毛膜祖细胞的早期BMP4信号传导是未分化的异位胎盘锥细胞正确分化所必需的，后来是它们向滋养层巨细胞分化所必需。研究人员还发现BMP4在胚胎中具有双相调节作用。早期源自ExE的BMP4信号对于中胚层的正常分叉以及尿囊和原始生殖细胞的鉴定是必要的。

然而，从胚胎第7.5天开始，胚胎来源的BMP4通过促进其胚胎外中胚层前体向尿囊命运分化来限制原始生殖细胞库的大小。因此，ExE和胚胎组织在时间、空间和信号轴上纠缠在一起，突显了它们在体内和体外综合理解和建模的重要性。

附：英文原文

Title: Temporal BMP4 effects on mouse embryonic and extraembryonic development

Author: Hadas, Ron, Rubinstein, Hernan, Mittnenzweig, Markus, Mayshar, Yoav, Ben-Yair, Raz, Cheng, Saifeng, Aguilera-Castrejon, Alejandro, Reines, Netta, Orenbuch, Ayelet-Hashahar, Lifshitz, Aviezer, Chen, Dong-Yuan, Elowitz, Michael B., Zernicka-Goetz, Magdalena, Hanna, Jacob H., Tanay, Amos, Stelzer, Yonatan

Issue&Volume: 2024-09-18

Abstract: The developing placenta, which in mice originates through the extraembryonic ectoderm (ExE), is essential for mammalian embryonic development. Yet unbiased characterization of the differentiation dynamics of the ExE and its interactions with the embryo proper remains incomplete. Here we develop a temporal single-cell model of mouse gastrulation that maps continuous and parallel differentiation in embryonic and extraembryonic lineages. This is matched with a three-way perturbation approach to target signalling from the embryo proper, the ExE alone, or both. We show that ExE specification involves early spatial and transcriptional bifurcation of uncommitted ectoplacental cone cells and chorion progenitors. Early BMP4 signalling from chorion progenitors is required for proper differentiation of uncommitted ectoplacental cone cells and later for their specification towards trophoblast giant cells. We also find biphasic regulation by BMP4 in the embryo. The early ExE-originating BMP4 signal is necessary for proper mesoendoderm bifurcation and for allantois and primordial germ cell specification. However, commencing at embryonic day 7.5, embryo-derived BMP4 restricts the primordial germ cell pool size by favouring differentiation of their extraembryonic mesoderm precursors towards an allantois fate. ExE and embryonic tissues are therefore entangled in time, space and signalling axes, highlighting the importance of their integrated understanding and modelling in vivo and in vitro.

DOI: 10.1038/s41586-024-07937-5

Source: https://www.nature.com/articles/s41586-024-07937-5