An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation
Systematic study of the regulatory mechanisms of Hematopoietic Stem Cell and Progenitor Cell (HSPC) self-renewal is fundamentally important for understanding hematopoiesis and for manipulating HSPCs for therapeutic purposes. Previously, we have characterized gene expression and identified important...
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| Veröffentlicht in: | Integrative biology (Cambridge) 2018-07, Vol.10 (7), p.390-405 |
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| creator | You, Yanan Cuevas-Diaz Duran, Raquel Jiang, Lihua Dong, Xiaomin Zong, Shan Snyder, Michael Wu, Jia Qian |
| description | Systematic study of the regulatory mechanisms of Hematopoietic Stem Cell and Progenitor Cell (HSPC) self-renewal is fundamentally important for understanding hematopoiesis and for manipulating HSPCs for therapeutic purposes. Previously, we have characterized gene expression and identified important transcription factors (TFs) regulating the switch between self-renewal and differentiation in a multipotent Hematopoietic Progenitor Cell (HPC) line, EML (Erythroid, Myeloid, and Lymphoid) cells. Herein, we report binding maps for additional TFs (SOX4 and STAT3) by using chromatin immunoprecipitation (ChIP)-Sequencing, to address the underlying mechanisms regulating self-renewal properties of lineage-CD34+ subpopulation (Lin-CD34+ EML cells). Furthermore, we applied the Assay for Transposase Accessible Chromatin (ATAC)-Sequencing to globally identify the open chromatin regions associated with TF binding in the self-renewing Lin-CD34+ EML cells. Mass spectrometry (MS) was also used to quantify protein relative expression levels. Finally, by integrating the protein-protein interaction database, we built an expanded transcriptional regulatory and interaction network. We found that MAPK (Mitogen-activated protein kinase) pathway and TGF-β/SMAD signaling pathway components were highly enriched among the binding targets of these TFs in Lin-CD34+ EML cells. The present study integrates regulatory information at multiple levels to paint a more comprehensive picture of the HSPC self-renewal mechanisms. |
| doi_str_mv | 10.1039/c8ib00059j |
| format | Article |
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Previously, we have characterized gene expression and identified important transcription factors (TFs) regulating the switch between self-renewal and differentiation in a multipotent Hematopoietic Progenitor Cell (HPC) line, EML (Erythroid, Myeloid, and Lymphoid) cells. Herein, we report binding maps for additional TFs (SOX4 and STAT3) by using chromatin immunoprecipitation (ChIP)-Sequencing, to address the underlying mechanisms regulating self-renewal properties of lineage-CD34+ subpopulation (Lin-CD34+ EML cells). Furthermore, we applied the Assay for Transposase Accessible Chromatin (ATAC)-Sequencing to globally identify the open chromatin regions associated with TF binding in the self-renewing Lin-CD34+ EML cells. Mass spectrometry (MS) was also used to quantify protein relative expression levels. Finally, by integrating the protein-protein interaction database, we built an expanded transcriptional regulatory and interaction network. We found that MAPK (Mitogen-activated protein kinase) pathway and TGF-β/SMAD signaling pathway components were highly enriched among the binding targets of these TFs in Lin-CD34+ EML cells. The present study integrates regulatory information at multiple levels to paint a more comprehensive picture of the HSPC self-renewal mechanisms.</description><identifier>ISSN: 1757-9694</identifier><identifier>EISSN: 1757-9708</identifier><identifier>DOI: 10.1039/c8ib00059j</identifier><identifier>PMID: 29892750</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Antigens, CD34 - metabolism ; Binding ; CD34 antigen ; Cell Differentiation ; Cell Line ; Cell Lineage ; Cell self-renewal ; Cells (biology) ; Chromatin ; Chromatin - chemistry ; Chromatin Immunoprecipitation ; Cluster Analysis ; Differentiation ; Erythroid Cells - cytology ; Gene expression ; Gene Expression Profiling ; Gene mapping ; Gene Regulatory Networks ; Hematopoiesis ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Humans ; Immunoprecipitation ; Kinases ; Lymphocytes - cytology ; MAP kinase ; Mass Spectrometry ; Mass spectroscopy ; Mice ; Myeloid Cells - cytology ; Progenitor cells ; Protein Interaction Mapping ; Protein kinase ; Proteins ; Regulatory mechanisms (biology) ; Signal Transduction ; Smad protein ; SOXC Transcription Factors - metabolism ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Stem cells ; Therapeutic applications ; Transcription factors ; Transcription Factors - metabolism ; Transposase</subject><ispartof>Integrative biology (Cambridge), 2018-07, Vol.10 (7), p.390-405</ispartof><rights>Copyright Royal Society of Chemistry 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-4e334bc95b7166c2a129cd442ea4d9f527bb9159d3b733de551b826b543e2e343</citedby><cites>FETCH-LOGICAL-c406t-4e334bc95b7166c2a129cd442ea4d9f527bb9159d3b733de551b826b543e2e343</cites><orcidid>0000-0002-6938-6648</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29892750$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>You, Yanan</creatorcontrib><creatorcontrib>Cuevas-Diaz Duran, Raquel</creatorcontrib><creatorcontrib>Jiang, Lihua</creatorcontrib><creatorcontrib>Dong, Xiaomin</creatorcontrib><creatorcontrib>Zong, Shan</creatorcontrib><creatorcontrib>Snyder, Michael</creatorcontrib><creatorcontrib>Wu, Jia Qian</creatorcontrib><title>An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation</title><title>Integrative biology (Cambridge)</title><addtitle>Integr Biol (Camb)</addtitle><description>Systematic study of the regulatory mechanisms of Hematopoietic Stem Cell and Progenitor Cell (HSPC) self-renewal is fundamentally important for understanding hematopoiesis and for manipulating HSPCs for therapeutic purposes. Previously, we have characterized gene expression and identified important transcription factors (TFs) regulating the switch between self-renewal and differentiation in a multipotent Hematopoietic Progenitor Cell (HPC) line, EML (Erythroid, Myeloid, and Lymphoid) cells. Herein, we report binding maps for additional TFs (SOX4 and STAT3) by using chromatin immunoprecipitation (ChIP)-Sequencing, to address the underlying mechanisms regulating self-renewal properties of lineage-CD34+ subpopulation (Lin-CD34+ EML cells). Furthermore, we applied the Assay for Transposase Accessible Chromatin (ATAC)-Sequencing to globally identify the open chromatin regions associated with TF binding in the self-renewing Lin-CD34+ EML cells. Mass spectrometry (MS) was also used to quantify protein relative expression levels. Finally, by integrating the protein-protein interaction database, we built an expanded transcriptional regulatory and interaction network. We found that MAPK (Mitogen-activated protein kinase) pathway and TGF-β/SMAD signaling pathway components were highly enriched among the binding targets of these TFs in Lin-CD34+ EML cells. The present study integrates regulatory information at multiple levels to paint a more comprehensive picture of the HSPC self-renewal mechanisms.</description><subject>Animals</subject><subject>Antigens, CD34 - metabolism</subject><subject>Binding</subject><subject>CD34 antigen</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Cell Lineage</subject><subject>Cell self-renewal</subject><subject>Cells (biology)</subject><subject>Chromatin</subject><subject>Chromatin - chemistry</subject><subject>Chromatin Immunoprecipitation</subject><subject>Cluster Analysis</subject><subject>Differentiation</subject><subject>Erythroid Cells - cytology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene mapping</subject><subject>Gene Regulatory Networks</subject><subject>Hematopoiesis</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Kinases</subject><subject>Lymphocytes - cytology</subject><subject>MAP kinase</subject><subject>Mass Spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mice</subject><subject>Myeloid Cells - cytology</subject><subject>Progenitor cells</subject><subject>Protein Interaction Mapping</subject><subject>Protein kinase</subject><subject>Proteins</subject><subject>Regulatory mechanisms (biology)</subject><subject>Signal Transduction</subject><subject>Smad protein</subject><subject>SOXC Transcription Factors - metabolism</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Stem cells</subject><subject>Therapeutic applications</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Transposase</subject><issn>1757-9694</issn><issn>1757-9708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkctuFDEQRS0EIg_Y8AHIEpsoUhM_2-0NUhgFSBSJDawt210946HHHmw3Uf4ehzwErMoqn7p1SxehN5S8p4TrMz8ERwiRevsMHVIlVacVGZ4_vnstDtBRKVtCekGIeIkOmB40U5Icos15xCFWWGdbYcTrOTk74wzrZbY15Vscod6k_AOnCW9g13r7FKAGj_cZ_JJLytjDPOMC89RliHDT5m0c8RimCVqjBltDiq_Qi8nOBV4_1GP0_dPFt9WX7vrr58vV-XXnBelrJ4Bz4byWTtG-98xSpv0oBAMrRj1JppzTVOqRO8X5CFJSN7DeScGBARf8GH24190vbgejbwaync0-h53NtybZYP79iWFj1umX6YlQmvImcPIgkNPPBUo1u1DuTrQR0lIMI1Lotkiqhr77D92mJcd2XqMUEaJvZKNO7ymfUykZpiczlJi7AM1quPz4J8CrBr_92_4T-pgY_w3OhJhe</recordid><startdate>20180716</startdate><enddate>20180716</enddate><creator>You, Yanan</creator><creator>Cuevas-Diaz Duran, Raquel</creator><creator>Jiang, Lihua</creator><creator>Dong, Xiaomin</creator><creator>Zong, Shan</creator><creator>Snyder, Michael</creator><creator>Wu, Jia Qian</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6938-6648</orcidid></search><sort><creationdate>20180716</creationdate><title>An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation</title><author>You, Yanan ; Cuevas-Diaz Duran, Raquel ; Jiang, Lihua ; Dong, Xiaomin ; Zong, Shan ; Snyder, Michael ; Wu, Jia Qian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-4e334bc95b7166c2a129cd442ea4d9f527bb9159d3b733de551b826b543e2e343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antigens, CD34 - metabolism</topic><topic>Binding</topic><topic>CD34 antigen</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Cell Lineage</topic><topic>Cell self-renewal</topic><topic>Cells (biology)</topic><topic>Chromatin</topic><topic>Chromatin - chemistry</topic><topic>Chromatin Immunoprecipitation</topic><topic>Cluster Analysis</topic><topic>Differentiation</topic><topic>Erythroid Cells - cytology</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene mapping</topic><topic>Gene Regulatory Networks</topic><topic>Hematopoiesis</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Kinases</topic><topic>Lymphocytes - cytology</topic><topic>MAP kinase</topic><topic>Mass Spectrometry</topic><topic>Mass spectroscopy</topic><topic>Mice</topic><topic>Myeloid Cells - cytology</topic><topic>Progenitor cells</topic><topic>Protein Interaction Mapping</topic><topic>Protein kinase</topic><topic>Proteins</topic><topic>Regulatory mechanisms (biology)</topic><topic>Signal Transduction</topic><topic>Smad protein</topic><topic>SOXC Transcription Factors - metabolism</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Stem cells</topic><topic>Therapeutic applications</topic><topic>Transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Transposase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>You, Yanan</creatorcontrib><creatorcontrib>Cuevas-Diaz Duran, Raquel</creatorcontrib><creatorcontrib>Jiang, Lihua</creatorcontrib><creatorcontrib>Dong, Xiaomin</creatorcontrib><creatorcontrib>Zong, Shan</creatorcontrib><creatorcontrib>Snyder, Michael</creatorcontrib><creatorcontrib>Wu, Jia Qian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Integrative biology (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>You, Yanan</au><au>Cuevas-Diaz Duran, Raquel</au><au>Jiang, Lihua</au><au>Dong, Xiaomin</au><au>Zong, Shan</au><au>Snyder, Michael</au><au>Wu, Jia Qian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation</atitle><jtitle>Integrative biology (Cambridge)</jtitle><addtitle>Integr Biol (Camb)</addtitle><date>2018-07-16</date><risdate>2018</risdate><volume>10</volume><issue>7</issue><spage>390</spage><epage>405</epage><pages>390-405</pages><issn>1757-9694</issn><eissn>1757-9708</eissn><abstract>Systematic study of the regulatory mechanisms of Hematopoietic Stem Cell and Progenitor Cell (HSPC) self-renewal is fundamentally important for understanding hematopoiesis and for manipulating HSPCs for therapeutic purposes. Previously, we have characterized gene expression and identified important transcription factors (TFs) regulating the switch between self-renewal and differentiation in a multipotent Hematopoietic Progenitor Cell (HPC) line, EML (Erythroid, Myeloid, and Lymphoid) cells. Herein, we report binding maps for additional TFs (SOX4 and STAT3) by using chromatin immunoprecipitation (ChIP)-Sequencing, to address the underlying mechanisms regulating self-renewal properties of lineage-CD34+ subpopulation (Lin-CD34+ EML cells). Furthermore, we applied the Assay for Transposase Accessible Chromatin (ATAC)-Sequencing to globally identify the open chromatin regions associated with TF binding in the self-renewing Lin-CD34+ EML cells. Mass spectrometry (MS) was also used to quantify protein relative expression levels. Finally, by integrating the protein-protein interaction database, we built an expanded transcriptional regulatory and interaction network. We found that MAPK (Mitogen-activated protein kinase) pathway and TGF-β/SMAD signaling pathway components were highly enriched among the binding targets of these TFs in Lin-CD34+ EML cells. The present study integrates regulatory information at multiple levels to paint a more comprehensive picture of the HSPC self-renewal mechanisms.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>29892750</pmid><doi>10.1039/c8ib00059j</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-6938-6648</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigens, CD34 - metabolism Binding CD34 antigen Cell Differentiation Cell Line Cell Lineage Cell self-renewal Cells (biology) Chromatin Chromatin - chemistry Chromatin Immunoprecipitation Cluster Analysis Differentiation Erythroid Cells - cytology Gene expression Gene Expression Profiling Gene mapping Gene Regulatory Networks Hematopoiesis Hematopoietic stem cells Hematopoietic Stem Cells - cytology Humans Immunoprecipitation Kinases Lymphocytes - cytology MAP kinase Mass Spectrometry Mass spectroscopy Mice Myeloid Cells - cytology Progenitor cells Protein Interaction Mapping Protein kinase Proteins Regulatory mechanisms (biology) Signal Transduction Smad protein SOXC Transcription Factors - metabolism Stat3 protein STAT3 Transcription Factor - metabolism Stem cells Therapeutic applications Transcription factors Transcription Factors - metabolism Transposase |
| title | An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation |
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