Transcriptional diversity during lineage commitment of human blood progenitors
Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stag...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2014-09, Vol.345 (6204), p.1580-1580 |
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| creator | Chen, Lu Kostadima, Myrto Martens, Joost H. A. Canu, Giovanni Garcia, Sara P. Turro, Ernest Downes, Kate Macaulay, Iain C. Bielczyk-Maczynska, Ewa Coe, Sophia Farrow, Samantha Poudel, Pawan Burden, Frances Jansen, Sjoert B. G. Astle, William J. Attwood, Antony Bariana, Tadbir de Bono, Bernard Breschi, Alessandra Chambers, John C. Consortium, BRIDGE Choudry, Fizzah A. Clarke, Laura Coupland, Paul van der Ent, Martijn Erber, Wendy N. Jansen, Joop H. Favier, Rémi Fenech, Matthew E. Foad, Nicola Freson, Kathleen van Geet, Chris Gomez, Keith Guigo, Roderic Hampshire, Daniel Kelly, Anne M. Kerstens, Hindrik H. D. Kooner, Jaspal S. Laffan, Michael Lentaigne, Claire Labalette, Charlotte Martin, Tiphaine Meacham, Stuart Mumford, Andrew Nürnberg, Sylvia Palumbo, Emilio van der Reijden, Bert A. Richardson, David Sammut, Stephen J. Slodkowicz, Greg Tamuri, Asif U. Vasquez, Louella Voss, Katrin Watt, Stephen Westbury, Sarah Flicek, Paul Loos, Remco Goldman, Nick Bertone, Paul Read, Randy J. Richardson, Sylvia Cvejic, Ana Soranzo, Nicole Ouwehand, Willem H. Stunnenberg, Hendrik G. Frontini, Mattia Rendon, Augusto |
| description | Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine. |
| doi_str_mv | 10.1126/science.1251033 |
| format | Article |
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A. ; Canu, Giovanni ; Garcia, Sara P. ; Turro, Ernest ; Downes, Kate ; Macaulay, Iain C. ; Bielczyk-Maczynska, Ewa ; Coe, Sophia ; Farrow, Samantha ; Poudel, Pawan ; Burden, Frances ; Jansen, Sjoert B. G. ; Astle, William J. ; Attwood, Antony ; Bariana, Tadbir ; de Bono, Bernard ; Breschi, Alessandra ; Chambers, John C. ; Consortium, BRIDGE ; Choudry, Fizzah A. ; Clarke, Laura ; Coupland, Paul ; van der Ent, Martijn ; Erber, Wendy N. ; Jansen, Joop H. ; Favier, Rémi ; Fenech, Matthew E. ; Foad, Nicola ; Freson, Kathleen ; van Geet, Chris ; Gomez, Keith ; Guigo, Roderic ; Hampshire, Daniel ; Kelly, Anne M. ; Kerstens, Hindrik H. D. ; Kooner, Jaspal S. ; Laffan, Michael ; Lentaigne, Claire ; Labalette, Charlotte ; Martin, Tiphaine ; Meacham, Stuart ; Mumford, Andrew ; Nürnberg, Sylvia ; Palumbo, Emilio ; van der Reijden, Bert A. ; Richardson, David ; Sammut, Stephen J. ; Slodkowicz, Greg ; Tamuri, Asif U. ; Vasquez, Louella ; Voss, Katrin ; Watt, Stephen ; Westbury, Sarah ; Flicek, Paul ; Loos, Remco ; Goldman, Nick ; Bertone, Paul ; Read, Randy J. ; Richardson, Sylvia ; Cvejic, Ana ; Soranzo, Nicole ; Ouwehand, Willem H. ; Stunnenberg, Hendrik G. ; Frontini, Mattia ; Rendon, Augusto</creator><creatorcontrib>Chen, Lu ; Kostadima, Myrto ; Martens, Joost H. A. ; Canu, Giovanni ; Garcia, Sara P. ; Turro, Ernest ; Downes, Kate ; Macaulay, Iain C. ; Bielczyk-Maczynska, Ewa ; Coe, Sophia ; Farrow, Samantha ; Poudel, Pawan ; Burden, Frances ; Jansen, Sjoert B. G. ; Astle, William J. ; Attwood, Antony ; Bariana, Tadbir ; de Bono, Bernard ; Breschi, Alessandra ; Chambers, John C. ; Consortium, BRIDGE ; Choudry, Fizzah A. ; Clarke, Laura ; Coupland, Paul ; van der Ent, Martijn ; Erber, Wendy N. ; Jansen, Joop H. ; Favier, Rémi ; Fenech, Matthew E. ; Foad, Nicola ; Freson, Kathleen ; van Geet, Chris ; Gomez, Keith ; Guigo, Roderic ; Hampshire, Daniel ; Kelly, Anne M. ; Kerstens, Hindrik H. D. ; Kooner, Jaspal S. ; Laffan, Michael ; Lentaigne, Claire ; Labalette, Charlotte ; Martin, Tiphaine ; Meacham, Stuart ; Mumford, Andrew ; Nürnberg, Sylvia ; Palumbo, Emilio ; van der Reijden, Bert A. ; Richardson, David ; Sammut, Stephen J. ; Slodkowicz, Greg ; Tamuri, Asif U. ; Vasquez, Louella ; Voss, Katrin ; Watt, Stephen ; Westbury, Sarah ; Flicek, Paul ; Loos, Remco ; Goldman, Nick ; Bertone, Paul ; Read, Randy J. ; Richardson, Sylvia ; Cvejic, Ana ; Soranzo, Nicole ; Ouwehand, Willem H. ; Stunnenberg, Hendrik G. ; Frontini, Mattia ; Rendon, Augusto ; BRIDGE Consortium</creatorcontrib><description>Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.</description><identifier>ISSN: 0036-8075</identifier><identifier>ISSN: 1095-9203</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1251033</identifier><identifier>PMID: 25258084</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Alternative Splicing ; Blood ; Blood cells ; Cell Lineage - genetics ; Cellular biology ; Coding ; Cèl·lules mare hematopoètiques ; Differentiation ; Empalmament alternatiu ; Enrichment ; Gene expression ; Genes ; Genetic Variation ; Hematopoesi ; Hematopoiesis - genetics ; hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Humans ; Immune systems ; Individualized Instruction ; llinatge cel·lular ; medicine ; NFI Transcription Factors - genetics ; NFI Transcription Factors - metabolism ; Populations ; RESEARCH ARTICLE SUMMARY ; Ribonucleic acid ; Ribonucleic acids ; RNA ; RNA-Binding Proteins - metabolism ; Thrombopoiesis - genetics ; transcription (genetics) ; Transcriptome ; Transcripts (Written Records)</subject><ispartof>Science (American Association for the Advancement of Science), 2014-09, Vol.345 (6204), p.1580-1580</ispartof><rights>Copyright © 2014 American Association for the Advancement of Science</rights><rights>Copyright © 2014, American Association for the Advancement of Science.</rights><rights>Copyright © 2014, American Association for the Advancement of Science</rights><rights>This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on vol. 345, num. 6204, 2014. DOI: 10.1126/science.1251033 info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c757t-16d35bcc2b22de6a47f5171d127070316d8240c76fb02ff4574771ca9d46407c3</citedby><cites>FETCH-LOGICAL-c757t-16d35bcc2b22de6a47f5171d127070316d8240c76fb02ff4574771ca9d46407c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24917692$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24917692$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,799,881,2871,2872,26951,27901,27902,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25258084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Lu</creatorcontrib><creatorcontrib>Kostadima, Myrto</creatorcontrib><creatorcontrib>Martens, Joost H. 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D.</creatorcontrib><creatorcontrib>Kooner, Jaspal S.</creatorcontrib><creatorcontrib>Laffan, Michael</creatorcontrib><creatorcontrib>Lentaigne, Claire</creatorcontrib><creatorcontrib>Labalette, Charlotte</creatorcontrib><creatorcontrib>Martin, Tiphaine</creatorcontrib><creatorcontrib>Meacham, Stuart</creatorcontrib><creatorcontrib>Mumford, Andrew</creatorcontrib><creatorcontrib>Nürnberg, Sylvia</creatorcontrib><creatorcontrib>Palumbo, Emilio</creatorcontrib><creatorcontrib>van der Reijden, Bert A.</creatorcontrib><creatorcontrib>Richardson, David</creatorcontrib><creatorcontrib>Sammut, Stephen J.</creatorcontrib><creatorcontrib>Slodkowicz, Greg</creatorcontrib><creatorcontrib>Tamuri, Asif U.</creatorcontrib><creatorcontrib>Vasquez, Louella</creatorcontrib><creatorcontrib>Voss, Katrin</creatorcontrib><creatorcontrib>Watt, Stephen</creatorcontrib><creatorcontrib>Westbury, Sarah</creatorcontrib><creatorcontrib>Flicek, Paul</creatorcontrib><creatorcontrib>Loos, Remco</creatorcontrib><creatorcontrib>Goldman, Nick</creatorcontrib><creatorcontrib>Bertone, Paul</creatorcontrib><creatorcontrib>Read, Randy J.</creatorcontrib><creatorcontrib>Richardson, Sylvia</creatorcontrib><creatorcontrib>Cvejic, Ana</creatorcontrib><creatorcontrib>Soranzo, Nicole</creatorcontrib><creatorcontrib>Ouwehand, Willem H.</creatorcontrib><creatorcontrib>Stunnenberg, Hendrik G.</creatorcontrib><creatorcontrib>Frontini, Mattia</creatorcontrib><creatorcontrib>Rendon, Augusto</creatorcontrib><creatorcontrib>BRIDGE Consortium</creatorcontrib><title>Transcriptional diversity during lineage commitment of human blood progenitors</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.</description><subject>Alternative Splicing</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Cell Lineage - genetics</subject><subject>Cellular biology</subject><subject>Coding</subject><subject>Cèl·lules mare hematopoètiques</subject><subject>Differentiation</subject><subject>Empalmament alternatiu</subject><subject>Enrichment</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic Variation</subject><subject>Hematopoesi</subject><subject>Hematopoiesis - genetics</subject><subject>hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Immune systems</subject><subject>Individualized Instruction</subject><subject>llinatge cel·lular</subject><subject>medicine</subject><subject>NFI Transcription Factors - genetics</subject><subject>NFI Transcription Factors - metabolism</subject><subject>Populations</subject><subject>RESEARCH ARTICLE SUMMARY</subject><subject>Ribonucleic acid</subject><subject>Ribonucleic acids</subject><subject>RNA</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Thrombopoiesis - genetics</subject><subject>transcription (genetics)</subject><subject>Transcriptome</subject><subject>Transcripts (Written Records)</subject><issn>0036-8075</issn><issn>1095-9203</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>XX2</sourceid><recordid>eNqFks1v1DAQxS0EokvhzAkUiQuXtDP-3FyQqqoFpAou5Ww5jrP1KrEXO6nU_x5vNywflx6syJrfjF_mPULeIpwhUnmerXfBujOkAoGxZ2SF0Ii6ocCekxUAk_UalDghr3LeApRaw16SEyqoWMOar8i322RCtsnvJh-DGarO37uU_fRQdXPyYVMNPjizcZWN4-in0YWpin11N48mVO0QY1ftUty44KeY8mvyojdDdm-W7yn5cX11e_mlvvn--evlxU1tlVBTjbJjorWWtpR2ThqueoEKO6QKFLBSXlMOVsm-Bdr3XCiuFFrTdFxyUJadkk-Hubu5HV1ni6pkBr1LfjTpQUfj9b-V4O_0Jt5rTgVXnJYBeBhg82x1ctYla6bHxuNlfygoqplQDcrS83F5NMWfs8uTHn22bhhMcHHOhS0LF7SofRLFBnjxCEA8jQopi6nY7AV8-A_dxjkV1wq1Zzjio8zz5ddSzDm5_rgWBL1PjV5So5fUlI73f2_zyP-OSQHeHYBtLi7_qfMGlWwo-wVon8f2</recordid><startdate>20140926</startdate><enddate>20140926</enddate><creator>Chen, Lu</creator><creator>Kostadima, Myrto</creator><creator>Martens, Joost H. 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A. ; Canu, Giovanni ; Garcia, Sara P. ; Turro, Ernest ; Downes, Kate ; Macaulay, Iain C. ; Bielczyk-Maczynska, Ewa ; Coe, Sophia ; Farrow, Samantha ; Poudel, Pawan ; Burden, Frances ; Jansen, Sjoert B. G. ; Astle, William J. ; Attwood, Antony ; Bariana, Tadbir ; de Bono, Bernard ; Breschi, Alessandra ; Chambers, John C. ; Consortium, BRIDGE ; Choudry, Fizzah A. ; Clarke, Laura ; Coupland, Paul ; van der Ent, Martijn ; Erber, Wendy N. ; Jansen, Joop H. ; Favier, Rémi ; Fenech, Matthew E. ; Foad, Nicola ; Freson, Kathleen ; van Geet, Chris ; Gomez, Keith ; Guigo, Roderic ; Hampshire, Daniel ; Kelly, Anne M. ; Kerstens, Hindrik H. D. ; Kooner, Jaspal S. ; Laffan, Michael ; Lentaigne, Claire ; Labalette, Charlotte ; Martin, Tiphaine ; Meacham, Stuart ; Mumford, Andrew ; Nürnberg, Sylvia ; Palumbo, Emilio ; van der Reijden, Bert A. ; Richardson, David ; Sammut, Stephen J. ; Slodkowicz, Greg ; Tamuri, Asif U. ; Vasquez, Louella ; Voss, Katrin ; Watt, Stephen ; Westbury, Sarah ; Flicek, Paul ; Loos, Remco ; Goldman, Nick ; Bertone, Paul ; Read, Randy J. ; Richardson, Sylvia ; Cvejic, Ana ; Soranzo, Nicole ; Ouwehand, Willem H. ; Stunnenberg, Hendrik G. ; Frontini, Mattia ; Rendon, Augusto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c757t-16d35bcc2b22de6a47f5171d127070316d8240c76fb02ff4574771ca9d46407c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alternative Splicing</topic><topic>Blood</topic><topic>Blood cells</topic><topic>Cell Lineage - genetics</topic><topic>Cellular biology</topic><topic>Coding</topic><topic>Cèl·lules mare hematopoètiques</topic><topic>Differentiation</topic><topic>Empalmament alternatiu</topic><topic>Enrichment</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic Variation</topic><topic>Hematopoesi</topic><topic>Hematopoiesis - genetics</topic><topic>hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Immune systems</topic><topic>Individualized Instruction</topic><topic>llinatge cel·lular</topic><topic>medicine</topic><topic>NFI Transcription Factors - genetics</topic><topic>NFI Transcription Factors - metabolism</topic><topic>Populations</topic><topic>RESEARCH ARTICLE SUMMARY</topic><topic>Ribonucleic acid</topic><topic>Ribonucleic acids</topic><topic>RNA</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Thrombopoiesis - genetics</topic><topic>transcription (genetics)</topic><topic>Transcriptome</topic><topic>Transcripts (Written Records)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Lu</creatorcontrib><creatorcontrib>Kostadima, Myrto</creatorcontrib><creatorcontrib>Martens, Joost H. A.</creatorcontrib><creatorcontrib>Canu, Giovanni</creatorcontrib><creatorcontrib>Garcia, Sara P.</creatorcontrib><creatorcontrib>Turro, Ernest</creatorcontrib><creatorcontrib>Downes, Kate</creatorcontrib><creatorcontrib>Macaulay, Iain C.</creatorcontrib><creatorcontrib>Bielczyk-Maczynska, Ewa</creatorcontrib><creatorcontrib>Coe, Sophia</creatorcontrib><creatorcontrib>Farrow, Samantha</creatorcontrib><creatorcontrib>Poudel, Pawan</creatorcontrib><creatorcontrib>Burden, Frances</creatorcontrib><creatorcontrib>Jansen, Sjoert B. G.</creatorcontrib><creatorcontrib>Astle, William J.</creatorcontrib><creatorcontrib>Attwood, Antony</creatorcontrib><creatorcontrib>Bariana, Tadbir</creatorcontrib><creatorcontrib>de Bono, Bernard</creatorcontrib><creatorcontrib>Breschi, Alessandra</creatorcontrib><creatorcontrib>Chambers, John C.</creatorcontrib><creatorcontrib>Consortium, BRIDGE</creatorcontrib><creatorcontrib>Choudry, Fizzah A.</creatorcontrib><creatorcontrib>Clarke, Laura</creatorcontrib><creatorcontrib>Coupland, Paul</creatorcontrib><creatorcontrib>van der Ent, Martijn</creatorcontrib><creatorcontrib>Erber, Wendy N.</creatorcontrib><creatorcontrib>Jansen, Joop H.</creatorcontrib><creatorcontrib>Favier, Rémi</creatorcontrib><creatorcontrib>Fenech, Matthew E.</creatorcontrib><creatorcontrib>Foad, Nicola</creatorcontrib><creatorcontrib>Freson, Kathleen</creatorcontrib><creatorcontrib>van Geet, Chris</creatorcontrib><creatorcontrib>Gomez, Keith</creatorcontrib><creatorcontrib>Guigo, Roderic</creatorcontrib><creatorcontrib>Hampshire, Daniel</creatorcontrib><creatorcontrib>Kelly, Anne M.</creatorcontrib><creatorcontrib>Kerstens, Hindrik H. D.</creatorcontrib><creatorcontrib>Kooner, Jaspal S.</creatorcontrib><creatorcontrib>Laffan, Michael</creatorcontrib><creatorcontrib>Lentaigne, Claire</creatorcontrib><creatorcontrib>Labalette, Charlotte</creatorcontrib><creatorcontrib>Martin, Tiphaine</creatorcontrib><creatorcontrib>Meacham, Stuart</creatorcontrib><creatorcontrib>Mumford, Andrew</creatorcontrib><creatorcontrib>Nürnberg, Sylvia</creatorcontrib><creatorcontrib>Palumbo, Emilio</creatorcontrib><creatorcontrib>van der Reijden, Bert A.</creatorcontrib><creatorcontrib>Richardson, David</creatorcontrib><creatorcontrib>Sammut, Stephen J.</creatorcontrib><creatorcontrib>Slodkowicz, Greg</creatorcontrib><creatorcontrib>Tamuri, Asif U.</creatorcontrib><creatorcontrib>Vasquez, Louella</creatorcontrib><creatorcontrib>Voss, Katrin</creatorcontrib><creatorcontrib>Watt, Stephen</creatorcontrib><creatorcontrib>Westbury, Sarah</creatorcontrib><creatorcontrib>Flicek, Paul</creatorcontrib><creatorcontrib>Loos, Remco</creatorcontrib><creatorcontrib>Goldman, Nick</creatorcontrib><creatorcontrib>Bertone, Paul</creatorcontrib><creatorcontrib>Read, Randy J.</creatorcontrib><creatorcontrib>Richardson, Sylvia</creatorcontrib><creatorcontrib>Cvejic, Ana</creatorcontrib><creatorcontrib>Soranzo, Nicole</creatorcontrib><creatorcontrib>Ouwehand, Willem H.</creatorcontrib><creatorcontrib>Stunnenberg, Hendrik G.</creatorcontrib><creatorcontrib>Frontini, Mattia</creatorcontrib><creatorcontrib>Rendon, Augusto</creatorcontrib><creatorcontrib>BRIDGE Consortium</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Lu</au><au>Kostadima, Myrto</au><au>Martens, Joost H. A.</au><au>Canu, Giovanni</au><au>Garcia, Sara P.</au><au>Turro, Ernest</au><au>Downes, Kate</au><au>Macaulay, Iain C.</au><au>Bielczyk-Maczynska, Ewa</au><au>Coe, Sophia</au><au>Farrow, Samantha</au><au>Poudel, Pawan</au><au>Burden, Frances</au><au>Jansen, Sjoert B. G.</au><au>Astle, William J.</au><au>Attwood, Antony</au><au>Bariana, Tadbir</au><au>de Bono, Bernard</au><au>Breschi, Alessandra</au><au>Chambers, John C.</au><au>Consortium, BRIDGE</au><au>Choudry, Fizzah A.</au><au>Clarke, Laura</au><au>Coupland, Paul</au><au>van der Ent, Martijn</au><au>Erber, Wendy N.</au><au>Jansen, Joop H.</au><au>Favier, Rémi</au><au>Fenech, Matthew E.</au><au>Foad, Nicola</au><au>Freson, Kathleen</au><au>van Geet, Chris</au><au>Gomez, Keith</au><au>Guigo, Roderic</au><au>Hampshire, Daniel</au><au>Kelly, Anne M.</au><au>Kerstens, Hindrik H. D.</au><au>Kooner, Jaspal S.</au><au>Laffan, Michael</au><au>Lentaigne, Claire</au><au>Labalette, Charlotte</au><au>Martin, Tiphaine</au><au>Meacham, Stuart</au><au>Mumford, Andrew</au><au>Nürnberg, Sylvia</au><au>Palumbo, Emilio</au><au>van der Reijden, Bert A.</au><au>Richardson, David</au><au>Sammut, Stephen J.</au><au>Slodkowicz, Greg</au><au>Tamuri, Asif U.</au><au>Vasquez, Louella</au><au>Voss, Katrin</au><au>Watt, Stephen</au><au>Westbury, Sarah</au><au>Flicek, Paul</au><au>Loos, Remco</au><au>Goldman, Nick</au><au>Bertone, Paul</au><au>Read, Randy J.</au><au>Richardson, Sylvia</au><au>Cvejic, Ana</au><au>Soranzo, Nicole</au><au>Ouwehand, Willem H.</au><au>Stunnenberg, Hendrik G.</au><au>Frontini, Mattia</au><au>Rendon, Augusto</au><aucorp>BRIDGE Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptional diversity during lineage commitment of human blood progenitors</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2014-09-26</date><risdate>2014</risdate><volume>345</volume><issue>6204</issue><spage>1580</spage><epage>1580</epage><pages>1580-1580</pages><issn>0036-8075</issn><issn>1095-9203</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Blood cells derive from hematopoietic stem cells through stepwise fating events. To characterize gene expression programs driving lineage choice, we sequenced RNA from eight primary human hematopoietic progenitor populations representing the major myeloid commitment stages and the main lymphoid stage. We identified extensive cell type-specific expression changes: 6711 genes and 10,724 transcripts, enriched in non-protein-coding elements at early stages of differentiation. In addition, we found 7881 novel splice junctions and 2301 differentially used alternative splicing events, enriched in genes involved in regulatory processes. We demonstrated experimentally cell-specific isoform usage, identifying nuclear factor I/B (NFIB) as a regulator of megakaryocyte maturation-the platelet precursor. Our data highlight the complexity of fating events in closely related progenitor populations, the understanding of which is essential for the advancement of transplantation and regenerative medicine.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>25258084</pmid><doi>10.1126/science.1251033</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2014-09, Vol.345 (6204), p.1580-1580 |
| issn | 0036-8075 1095-9203 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4254742 |
| source | American Association for the Advancement of Science; Jstor Complete Legacy; MEDLINE; Recercat |
| subjects | Alternative Splicing Blood Blood cells Cell Lineage - genetics Cellular biology Coding Cèl·lules mare hematopoètiques Differentiation Empalmament alternatiu Enrichment Gene expression Genes Genetic Variation Hematopoesi Hematopoiesis - genetics hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Humans Immune systems Individualized Instruction llinatge cel·lular medicine NFI Transcription Factors - genetics NFI Transcription Factors - metabolism Populations RESEARCH ARTICLE SUMMARY Ribonucleic acid Ribonucleic acids RNA RNA-Binding Proteins - metabolism Thrombopoiesis - genetics transcription (genetics) Transcriptome Transcripts (Written Records) |
| title | Transcriptional diversity during lineage commitment of human blood progenitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T00%3A42%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Transcriptional%20diversity%20during%20lineage%20commitment%20of%20human%20blood%20progenitors&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Chen,%20Lu&rft.aucorp=BRIDGE%20Consortium&rft.date=2014-09-26&rft.volume=345&rft.issue=6204&rft.spage=1580&rft.epage=1580&rft.pages=1580-1580&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.1251033&rft_dat=%3Cjstor_pubme%3E24917692%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1610941116&rft_id=info:pmid/25258084&rft_jstor_id=24917692&rfr_iscdi=true |