Open AccessIntercellular network structure and regulatory motifs in the human hematopoietic system
Author(s) -
Qiao Wenlian,
Wang Weijia,
Laurenti Elisa,
Turinsky Andrei L,
Wodak Shoshana J,
Bader Gary D,
Dick John E,
Zandstra Peter W
Publication year - 2014
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20145141
Subject(s) - biology , microbiology and biotechnology , cell fate determination , haematopoiesis , hematopoietic stem cell , cell type , intracellular , cell , multicellular organism , cellular differentiation , stem cell , transcription factor , genetics , gene
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.