英国剑桥大学Thorsten E. Boroviak课题组发现，狒狒和人类滋养层干细胞在信号需求上存在差异，并重现不同的滋养层侵袭模式。该研究于2024年9月24日在线发表于国际一流学术期刊《细胞—干细胞》。

研究人员在表面植入的狒狒胚胎中追踪了滋养层谱系的植入前到植入后的过渡。研究人员将狒狒的初始多能干细胞分化为滋养层干细胞（TSC），这些细胞表现出滋养层特异的转录组、甲基组、分化潜能和长期自我更新能力。值得注意的是，人类TSC的培养条件未能支持狒狒TSC的衍生，反而诱导狒狒细胞向类似胚外中胚层的命运转变。

结果表明，联合MEK、TGF-β/NODAL和组蛋白去乙酰化酶抑制可以稳定狒狒TSC中的植入期滋养层样身份。相比之下，这些条件则使人类TSC向外滋养层细胞分化。该研究提供了一种范式，可利用植入策略的演化差异来阐明人类滋养层的发育和侵袭机制。

据了解，早期人类滋养层发育一直难以捉摸，主要由于早期胚胎的不可获取。非人类灵长类动物模型重现了人类发育的许多特征，并允许研究早期植入后阶段。

附：英文原文

Title: Marmoset and human trophoblast stem cells differ in signaling requirements and recapitulate divergent modes of trophoblast invasion

Author: Dylan Siriwardena, Clara Munger, Christopher Penfold, Timo N. Kohler, Antonia Weberling, Madeleine Linneberg-Agerholm, Erin Slatery, Anna L. Ellermann, Sophie Bergmann, Stephen J. Clark, Thomas M. Rawlings, Joshua M. Brickman, Wolf Reik, Jan J. Brosens, Magdalena Zernicka-Goetz, Erika Sasaki, Rüdiger Behr, Florian Hollfelder, Thorsten E. Boroviak

Issue&Volume: 2024-09-24

Abstract: Early human trophoblast development has remained elusive due to the inaccessibility of the early conceptus. Non-human primate models recapitulate many features of human development and allow access to early postimplantation stages. Here, we tracked the pre- to postimplantation transition of the trophoblast lineage in superficially implanting marmoset embryos in vivo. We differentiated marmoset naive pluripotent stem cells into trophoblast stem cells (TSCs), which exhibited trophoblast-specific transcriptome, methylome, differentiation potential, and long-term self-renewal. Notably, human TSC culture conditions failed to support marmoset TSC derivation, instead inducing an extraembryonic mesoderm-like fate in marmoset cells. We show that combined MEK, TGF-β/NODAL, and histone deacetylase inhibition stabilizes a periimplantation trophoblast-like identity in marmoset TSCs. By contrast, these conditions differentiated human TSCs toward extravillous trophoblasts. Our work presents a paradigm to harness the evolutionary divergence in implantation strategies to elucidate human trophoblast development and invasion.

DOI: 10.1016/j.stem.2024.09.004

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00318-7