CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development

Autor: Lummertz da Rocha, Edroaldo, Kubaczka, Caroline, Sugden, Wade W., Najia, Mohamad Ali, Jing, Ran, Markel, Arianna, LeBlanc, Zachary C., dos Santos Peixoto, Rafael, Falchetti, Marcelo, Collins, James J., North, Trista E., Daley, George Q.
Zdroj: Nature Cell Biology; April 2022, Vol. 24 Issue: 4 p579-589, 11p
Abstrakt: 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, Ybx1and 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.
Databáze: Supplemental Index