CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development
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CellComm_70362_1_merged_1646329678_v2.pdf
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Accepted version
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15.4 MB
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Author(s) • • • • • • • • •
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
Date Issued
2022
Journal
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Citation
Lummertz da Rocha, Edroaldo, Kubaczka, Caroline, Sugden, Wade W, Najia, Mohamad Ali, Jing, Ran et al. 2022. "CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development." Nature Cell Biology, 24 (4).
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1038/S41556-022-00884-1