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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Qiao, Wenlian 
Wang, Weijia 
Turinsky, Andrei L 
Wodak, Shoshana J 

Abstract

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.

Description

Keywords

feedback regulation, hematopoietic stem cell, intercellular signaling, Algorithms, Cell Communication, Cells, Cultured, Gene Expression Profiling, Hematopoiesis, Hematopoietic Stem Cells, Humans, Ligands

Journal Title

Mol Syst Biol

Conference Name

Journal ISSN

1744-4292
1744-4292

Volume Title

10

Publisher

Springer Science and Business Media LLC