Intercellular network structure and regulatory motifs in the human hematopoietic system
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 communic...
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| Format: | Article |
| Language: | English |
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Springer Nature
2014-07-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20145141 |
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| author | Wenlian Qiao Weijia Wang Elisa Laurenti Andrei L Turinsky Shoshana J Wodak Gary D Bader John E Dick Peter W Zandstra |
| author_facet | Wenlian Qiao Weijia Wang Elisa Laurenti Andrei L Turinsky Shoshana J Wodak Gary D Bader John E Dick Peter W Zandstra |
| author_sort | Wenlian Qiao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-691d206a2b564fdf948695529598fe7f |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2014-07-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-691d206a2b564fdf948695529598fe7f2025-08-20T03:43:34ZengSpringer NatureMolecular Systems Biology1744-42922014-07-0110711810.15252/msb.20145141Intercellular network structure and regulatory motifs in the human hematopoietic systemWenlian Qiao0Weijia Wang1Elisa Laurenti2Andrei L Turinsky3Shoshana J Wodak4Gary D Bader5John E Dick6Peter W Zandstra7Institute of Biomaterials and Biomedical Engineering, University of TorontoInstitute of Biomaterials and Biomedical Engineering, University of TorontoPrincess Margaret Cancer Centre, University Health NetworkThe Hospital for Sick ChildrenThe Hospital for Sick ChildrenDepartment of Molecular Genetics, University of TorontoPrincess Margaret Cancer Centre, University Health NetworkInstitute of Biomaterials and Biomedical Engineering, University of TorontoAbstract 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.https://doi.org/10.15252/msb.20145141feedback regulationhematopoietic stem cellintercellular signaling |
| spellingShingle | Wenlian Qiao Weijia Wang Elisa Laurenti Andrei L Turinsky Shoshana J Wodak Gary D Bader John E Dick Peter W Zandstra Intercellular network structure and regulatory motifs in the human hematopoietic system Molecular Systems Biology feedback regulation hematopoietic stem cell intercellular signaling |
| title | Intercellular network structure and regulatory motifs in the human hematopoietic system |
| title_full | Intercellular network structure and regulatory motifs in the human hematopoietic system |
| title_fullStr | Intercellular network structure and regulatory motifs in the human hematopoietic system |
| title_full_unstemmed | Intercellular network structure and regulatory motifs in the human hematopoietic system |
| title_short | Intercellular network structure and regulatory motifs in the human hematopoietic system |
| title_sort | intercellular network structure and regulatory motifs in the human hematopoietic system |
| topic | feedback regulation hematopoietic stem cell intercellular signaling |
| url | https://doi.org/10.15252/msb.20145141 |
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