英国弗朗西斯克里克研究所James Briscoe和Tiago Rito共同合作，近期取得重要工作进展。他们研究提出，及时抑制TGFβ信号传导可诱导脊索发生。相关研究成果2024年12月18日在线发表于《自然》杂志上。

据介绍，脊椎动物身体的形成涉及位于胚胎后部的祖细胞协调产生躯干组织。尽管使用多能干细胞的体外模型复制了这一过程的各个方面。它们缺乏关键的组成部分，最明显的是脊索，脊索是脊索动物在组织周围形成图案的决定性特征。因此，目前的人体躯干形成模型中没有依赖于脊索信号的细胞类型。

研究人员对鸡胚进行了单细胞转录组分析，以绘制分子上不同的祖细胞群体及其空间组织。在图谱的指导下，研究人员分析了分化的人类多能干细胞如何形成躯干细胞类型的刻板空间组织。研究人员发现，YAP失活结合FGF介导的MAPK信号传导促进了WNT通路的激活，并诱导了TBXT（也称为BRA）的表达。

此外，及时抑制WNT诱导的NODAL和BMP信号传导调节了不同组织类型的比例，包括脊索细胞。这使研究人员能够创建一个人体躯干发育的三维模型，该模型经历形态发生运动，产生具有脊索、腹侧神经和中胚层组织的细长结构。

总之，这一研究结果为脊椎动物脊索形成的机制提供了见解，并建立了更全面的人体躯干发育体外模型。这为未来在生理相关环境中研究组织模式提供了指导。

附：英文原文

Title: Timely TGFβ signalling inhibition induces notochord

Author: Rito, Tiago, Libby, Ashley R. G., Demuth, Madeleine, Domart, Marie-Charlotte, Cornwall-Scoones, Jake, Briscoe, James

Issue&Volume: 2024-12-18

Abstract: The formation of the vertebrate body involves the coordinated production of trunk tissues from progenitors located in the posterior of the embryo. Although in vitro models using pluripotent stem cells replicate aspects of this process1,2,3,4,5,6,7,8,9,10, they lack crucial components, most notably the notochord—a defining feature of chordates that patterns surrounding tissues11. Consequently, cell types dependent on notochord signals are absent from current models of human trunk formation. Here we performed single-cell transcriptomic analysis of chick embryos to map molecularly distinct progenitor populations and their spatial organization. Guided by this map, we investigated how differentiating human pluripotent stem cells develop a stereotypical spatial organization of trunk cell types. We found that YAP inactivation in conjunction with FGF-mediated MAPK signalling facilitated WNT pathway activation and induced expression of TBXT (also known as BRA). In addition, timely inhibition of WNT-induced NODAL and BMP signalling regulated the proportions of different tissue types, including notochordal cells. This enabled us to create a three-dimensional model of human trunk development that undergoes morphogenetic movements, producing elongated structures with a notochord and ventral neural and mesodermal tissues. Our findings provide insights into the mechanisms underlying vertebrate notochord formation and establish a more comprehensive in vitro model of human trunk development. This paves the way for future studies of tissue patterning in a physiologically relevant environment.

DOI: 10.1038/s41586-024-08332-w

Source: https://www.nature.com/articles/s41586-024-08332-w