Dynamic interaction networks in a hierarchically organized tissue
Abstract Intercellular (between cell) communication networks maintain homeostasis and coordinate regenerative and developmental cues in multicellular organisms. Despite the importance of intercellular networks in stem cell biology, their rules, structure and molecular components are poorly understoo...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2010-10-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.1038/msb.2010.71 |
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| _version_ | 1849225763397566464 |
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| author | Daniel C Kirouac Caryn Ito Elizabeth Csaszar Aline Roch Mei Yu Edward A Sykes Gary D Bader Peter W Zandstra |
| author_facet | Daniel C Kirouac Caryn Ito Elizabeth Csaszar Aline Roch Mei Yu Edward A Sykes Gary D Bader Peter W Zandstra |
| author_sort | Daniel C Kirouac |
| collection | DOAJ |
| description | Abstract Intercellular (between cell) communication networks maintain homeostasis and coordinate regenerative and developmental cues in multicellular organisms. Despite the importance of intercellular networks in stem cell biology, their rules, structure and molecular components are poorly understood. Herein, we describe the structure and dynamics of intercellular and intracellular networks in a stem cell derived, hierarchically organized tissue using experimental and theoretical analyses of cultured human umbilical cord blood progenitors. By integrating high‐throughput molecular profiling, database and literature mining, mechanistic modeling, and cell culture experiments, we show that secreted factor‐mediated intercellular communication networks regulate blood stem cell fate decisions. In particular, self‐renewal is modulated by a coupled positive–negative intercellular feedback circuit composed of megakaryocyte‐derived stimulatory growth factors (VEGF, PDGF, EGF, and serotonin) versus monocyte‐derived inhibitory factors (CCL3, CCL4, CXCL10, TGFB2, and TNFSF9). We reconstruct a stem cell intracellular network, and identify PI3K, Raf, Akt, and PLC as functionally distinct signal integration nodes, linking extracellular, and intracellular signaling. This represents the first systematic characterization of how stem cell fate decisions are regulated non‐autonomously through lineage‐specific interactions with differentiated progeny. |
| format | Article |
| id | doaj-art-58beec843042450bbc1c0ff43879ba37 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2010-10-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-58beec843042450bbc1c0ff43879ba372025-08-24T12:00:37ZengSpringer NatureMolecular Systems Biology1744-42922010-10-016111610.1038/msb.2010.71Dynamic interaction networks in a hierarchically organized tissueDaniel C Kirouac0Caryn Ito1Elizabeth Csaszar2Aline Roch3Mei Yu4Edward A Sykes5Gary D Bader6Peter W Zandstra7Institute for Biomaterials and Biomedical Engineering, University of TorontoInstitute for Biomaterials and Biomedical Engineering, University of TorontoInstitute for Biomaterials and Biomedical Engineering, University of TorontoEcole Polytechnique Fédérale de LausanneInstitute for Biomaterials and Biomedical Engineering, University of TorontoInstitute for Biomaterials and Biomedical Engineering, University of TorontoTerrence Donnelly Centre for Cellular and Biomolecular Research, University of TorontoInstitute for Biomaterials and Biomedical Engineering, University of TorontoAbstract Intercellular (between cell) communication networks maintain homeostasis and coordinate regenerative and developmental cues in multicellular organisms. Despite the importance of intercellular networks in stem cell biology, their rules, structure and molecular components are poorly understood. Herein, we describe the structure and dynamics of intercellular and intracellular networks in a stem cell derived, hierarchically organized tissue using experimental and theoretical analyses of cultured human umbilical cord blood progenitors. By integrating high‐throughput molecular profiling, database and literature mining, mechanistic modeling, and cell culture experiments, we show that secreted factor‐mediated intercellular communication networks regulate blood stem cell fate decisions. In particular, self‐renewal is modulated by a coupled positive–negative intercellular feedback circuit composed of megakaryocyte‐derived stimulatory growth factors (VEGF, PDGF, EGF, and serotonin) versus monocyte‐derived inhibitory factors (CCL3, CCL4, CXCL10, TGFB2, and TNFSF9). We reconstruct a stem cell intracellular network, and identify PI3K, Raf, Akt, and PLC as functionally distinct signal integration nodes, linking extracellular, and intracellular signaling. This represents the first systematic characterization of how stem cell fate decisions are regulated non‐autonomously through lineage‐specific interactions with differentiated progeny.https://doi.org/10.1038/msb.2010.71cellular networkshematopoiesisintercellular signalingself‐renewalstem cells |
| spellingShingle | Daniel C Kirouac Caryn Ito Elizabeth Csaszar Aline Roch Mei Yu Edward A Sykes Gary D Bader Peter W Zandstra Dynamic interaction networks in a hierarchically organized tissue Molecular Systems Biology cellular networks hematopoiesis intercellular signaling self‐renewal stem cells |
| title | Dynamic interaction networks in a hierarchically organized tissue |
| title_full | Dynamic interaction networks in a hierarchically organized tissue |
| title_fullStr | Dynamic interaction networks in a hierarchically organized tissue |
| title_full_unstemmed | Dynamic interaction networks in a hierarchically organized tissue |
| title_short | Dynamic interaction networks in a hierarchically organized tissue |
| title_sort | dynamic interaction networks in a hierarchically organized tissue |
| topic | cellular networks hematopoiesis intercellular signaling self‐renewal stem cells |
| url | https://doi.org/10.1038/msb.2010.71 |
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