Nature Cell Biology ( IF 17.3 ) Pub Date : 2024-10-02 , DOI: 10.1038/s41556-024-01521-9 Harold M. McNamara, Sabrina C. Solley, Britt Adamson, Michelle M. Chan, Jared E. Toettcher
Aggregates of stem cells can break symmetry and self-organize into embryo-like structures with complex morphologies and gene expression patterns. Mechanisms including reaction-diffusion Turing patterns and cell sorting have been proposed to explain symmetry breaking but distinguishing between these candidate mechanisms of self-organization requires identifying which early asymmetries evolve into subsequent tissue patterns and cell fates. Here we use synthetic ‘signal-recording’ gene circuits to trace the evolution of signalling patterns in gastruloids, three-dimensional stem cell aggregates that form an anterior–posterior axis and structures resembling the mammalian primitive streak and tailbud. We find that cell sorting rearranges patchy domains of Wnt activity into a single pole that defines the gastruloid anterior–posterior axis. We also trace the emergence of Wnt domains to earlier heterogeneity in Nodal activity even before Wnt activity is detectable. Our study defines a mechanism through which aggregates of stem cells can form a patterning axis even in the absence of external spatial cues.
中文翻译:
记录形态发生素信号揭示了原粒样对称性破坏的机制
干细胞的聚集体可以打破对称性并自组织成具有复杂形态和基因表达模式的胚胎样结构。包括反应-扩散、图灵模式和细胞分选在内的机制已被提出来解释对称性破坏,但区分这些候选的自组织机制需要确定哪些早期不对称演变成随后的组织模式和细胞命运。在这里,我们使用合成的“信号记录”基因电路来追踪原肠类中信号模式的进化,原状体是形成前后轴的三维干细胞聚集体和类似于哺乳动物原始条纹和尾芽的结构。我们发现细胞分选将 Wnt 活性的斑片结构域重新排列到定义原状前轴-后轴的单个极点。我们还将 Wnt 结构域的出现追溯到 Wnt 活性的早期异质性,甚至在可检测到 Wnt 活性之前。我们的研究定义了一种机制,即使没有外部空间线索,干细胞的聚集体也可以形成模式轴。