CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development.
Edroaldo Lummertz da Rocha, Caroline Kubaczka, Wade W Sugden, Mohamad Ali Najia, Ran Jing, Arianna Markel, Zachary C LeBlanc, Rafael Dos Santos Peixoto, Marcelo Falchetti, James J Collins, Trista E North, George Q Daley
Author Information
Edroaldo Lummertz da Rocha: Department of Microbiology, Immunology and Parasitology, Federal University of Santa Catarina, Florian��polis, Brazil. ORCID
Caroline Kubaczka: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. ORCID
Wade W Sugden: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. ORCID
Mohamad Ali Najia: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. ORCID
Ran Jing: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. ORCID
Arianna Markel: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA.
Zachary C LeBlanc: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. ORCID
Rafael Dos Santos Peixoto: Undergraduate program in Automation and Control Engineering, Federal University of Santa Catarina, Florian��polis, Brazil. ORCID
Marcelo Falchetti: Graduate Program of Pharmacology, Center for Biological Sciences, Federal University of Santa Catarina, Florian��polis, Brazil. ORCID
James J Collins: Broad Institute of MIT and Harvard, Cambridge, MA, USA. ORCID
Trista E North: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. trista.north@childrens.harvard.edu.
George Q Daley: Stem Cell Program, Boston Children's Hospital, Boston, MA, USA. George.Daley@childrens.harvard.edu. ORCID
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.
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