英国弗朗西斯·克里克研究所Silvia D.M. Santos团队的研究发现，GATA3介导人类胚胎干细胞（hESCs）中BMP4驱动分化的快速、不可逆的应答。相关论文发表在2020年4月16日出版的《细胞-干细胞》杂志上。

通过将单细胞成像、基因组方法和数学建模相结合，他们发现hESC容易意外失去多能性。他们表明，骨形态发生蛋白4（BMP4），一个重要的分化触发因素，诱导早期基因的一个亚群，以反映上游信号的持续的、双稳态的动力学。

在没有BMP4的情况下，这些基因之一GATA3的诱导驱动分化。相反，GATA3基因敲除延迟了分化并阻止了对分化的快速应答。他们表明，在GATA3-BMP4轴水平上的正反馈会诱导快速、不可逆的分化应答。

他们建议，早期应答可能是BMP驱动的命运选择的特征，而相互联系的反馈则是从多能性到分化不可逆转的分子基础。

据了解，在早期发育中，外在触发因素促使多能细胞开始分化过程。hESCs何时以及如何不可逆地进行分化是一个基本但尚未得到回答的问题。

附：英文原文

Title: GATA3 Mediates a Fast, Irreversible Commitment to BMP4-Driven Differentiation in Human Embryonic Stem Cells

Author: Alexandra Gunne-Braden, Adrienne Sullivan, Borzo Gharibi, Rahuman S.M. Sheriff, Alok Maity, Yi-Fang Wang, Amelia Edwards, Ming Jiang, Michael Howell, Robert Goldstone, Roy Wollman, Philip East, Silvia D.M. Santos

Issue&Volume: 2020-04-16

Abstract: During early development, extrinsic triggers prompt pluripotent cells to begin theprocess of differentiation. When and how human embryonic stem cells (hESCs) irreversiblycommit to differentiation is a fundamental yet unanswered question. By combining single-cellimaging, genomic approaches, and mathematical modeling, we find that hESCs committo exiting pluripotency unexpectedly early. We show that bone morphogenetic protein4 (BMP4), an important differentiation trigger, induces a subset of early genes tomirror the sustained, bistable dynamics of upstream signaling. Induction of one ofthese genes, GATA3, drives differentiation in the absence of BMP4. Conversely, GATA3knockout delays differentiation and prevents fast commitment to differentiation. Weshow that positive feedback at the level of the GATA3-BMP4 axis induces fast, irreversiblecommitment to differentiation. We propose that early commitment may be a feature ofBMP-driven fate choices and that interlinked feedback is the molecular basis for anirreversible transition from pluripotency to differentiation.

DOI: 10.1016/j.stem.2020.03.005

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30097-7