Intercellular network structure and regulatory motifs in the human hematopoietic system.

TitleIntercellular network structure and regulatory motifs in the human hematopoietic system.
Publication TypeJournal Article
Year of Publication2014
AuthorsQiao, W., W. Wang, E. Laurenti, A. L. Turinsky, S. J. Wodak, G. D. Bader, J. E. Dick, and P. W. Zandstra
JournalMol Syst Biol
Date Published2014 Jul 15
KeywordsAlgorithms, Cell Communication, Cells, Cultured, Gene Expression Profiling, Hematopoiesis, Hematopoietic Stem Cells, Humans, Ligands

The hematopoietic system is a distributed tissue that consists of functionally distinct cell types continuously produced through hematopoietic stem cell (HSC) differentiation. Combining genomic and phenotypic data with high-content experiments, we have built a directional cell-cell communication network between 12 cell types isolated from human umbilical cord blood. Network structure analysis revealed that ligand production is cell type dependent, whereas ligand binding is promiscuous. Consequently, additional control strategies such as cell frequency modulation and compartmentalization were needed to achieve specificity in HSC fate regulation. Incorporating the in vitro effects (quiescence, self-renewal, proliferation, or differentiation) of 27 HSC binding ligands into the topology of the cell-cell communication network allowed coding of cell type-dependent feedback regulation of HSC fate. Pathway enrichment analysis identified intracellular regulatory motifs enriched in these cell type- and ligand-coupled responses. This study uncovers cellular mechanisms of hematopoietic cell feedback in HSC fate regulation, provides insight into the design principles of the human hematopoietic system, and serves as a foundation for the analysis of intercellular regulation in multicellular systems.

Alternate JournalMol. Syst. Biol.
PubMed ID25028490
PubMed Central IDPMC4299490
Grant ListP41 GM103504 / GM / NIGMS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
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