美国洛克菲勒大学Ali H. Brivanlou课题组取得一项新突破。他们发现了组织力学和BMP4信号之间的串扰调节人原肠模型中的对称性破坏。相关论文于2025年10月13日发表于国际顶尖学术期刊《细胞—干细胞》杂志上。

该研究组开发了一种光诱导策略，在人类多能干细胞中诱导具有精确空间坐标的BMP4信号。光控BMP4诱导SMAD1-5磷酸化，导致羊膜分化，并依赖于WNT和NODAL的张力依赖性诱导中胚层分化。为了响应BMP4信号，机械敏感转录因子YAP1在核核中积累，在那里它抑制WNT3 mRNA，调节三个胚层的诱导。基于这些发现，研究小组建立了一个数学模型，将组织力学与形态动力学相结合，定量解释了BMP4信号在组织尺度上的反应。因此，在人干细胞模型中，光诱导形态原BMP4阐明了组织力学与原肠胚形成开始时信号传导之间的相互作用。

据介绍，形态发生信号的时空调控与局部组织力学一起，指导形态发生并决定胚胎的形状。然而，这些信号如何整合到发育回路中仍然知之甚少。

附：英文原文

Title: Crosstalk between tissue mechanics and BMP4 signaling regulates symmetry breaking in human gastrula models

Author: Riccardo De Santis, Laurent Jutras-Dubé, Sophia Bourdrel, Eleni Rice, Francesco M. Piccolo, Ali H. Brivanlou

Issue&Volume: 2025-10-13

Abstract: The spatiotemporal regulation of morphogenetic signals, along with local tissue mechanics, guides morphogenesis and determines the shape of the embryo. However, how these signals integrate into developmental circuits remains poorly understood. Here, we developed a light-inducible strategy to induce BMP4 signaling with precise spatial coordinates in human pluripotent stem cells. Light-controlled BMP4 induces SMAD1–5 phosphorylation, resulting in amnion differentiation, and relies on a tension-dependent induction of WNT and NODAL for mesoderm differentiation. In response to BMP4 signaling, the mechanosensitive transcription factor YAP1 accumulates in the nucleus, where it represses WNT3 mRNA, regulating the induction of the three germ layers. Based on these findings, we developed a mathematical model that integrates tissue mechanics into morphogen dynamics, quantitatively explaining tissue-scale responses to BMP4 signaling. Thus, light induction of the morphogen BMP4 in human stem cell models elucidated the interplay between tissue mechanics and signaling at the onset of gastrulation.

DOI: 10.1016/j.stem.2025.09.006

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00337-6