Intercellular communication orchestrates a multitude of physiologic and pathologic conditions. Algorithms to infer cell–cell communication and predict downstream signalling and regulatory networks are needed to illuminate mechanisms of stem cell differentiation and tissue development. Here, to fill this gap, we developed and applied CellComm to investigate how the aorta–gonad–mesonephros microenvironment dictates haematopoietic stem and progenitor cell emergence. We identified key microenvironmental signals and transcriptional networks that regulate haematopoietic development, including Stat3, Nr0b2, Ybx1 and App, and confirmed their roles using zebrafish, mouse and human models. Notably, CellComm revealed extensive crosstalk among signalling pathways and convergence on common transcriptional regulators, indicating a resilient developmental programme that ensures dynamic adaptation to changes in the embryonic environment. Our work provides an algorithm and data resource for the scientific community.

细胞间通讯协调多种生理和病理条件。需要推断细胞间通讯并预测下游信号和调节网络的算法来阐明干细胞分化和组织发育的机制。为了填补这一空白，我们开发并应用 CellComm 来研究主动脉-性腺-中肾微环境如何决定造血干细胞和祖细胞的出现。我们确定了调节造血发育的关键微环境信号和转录网络，包括Stat3 、 Nr0b2 、 Ybx1和App ，并使用斑马鱼、小鼠和人类模型证实了它们的作用。值得注意的是，CellComm 揭示了信号通路之间的广泛串扰以及常见转录调节因子的趋同，表明有一个弹性的发育程序，可确保动态适应胚胎环境的变化。我们的工作为科学界提供了算法和数据资源。