Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation: In memoriam Professor Niels Borregaard
Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this f...
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Veröffentlicht in: | Nature communications 2022-06, Vol.13 (1), p.3595-3595, Article 3595 |
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creator | Theilgaard-Mönch, Kim Pundhir, Sachin Reckzeh, Kristian Su, Jinyu Tapia, Marta Furtwängler, Benjamin Jendholm, Johan Jakobsen, Janus Schou Hasemann, Marie Sigurd Knudsen, Kasper Jermiin Cowland, Jack Bernard Fossum, Anna Schoof, Erwin Schuster, Mikkel Bruhn Porse, Bo T. |
description | Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of
Cdk1/2/4
inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.
Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation. |
doi_str_mv | 10.1038/s41467-022-31332-1 |
format | Article |
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Cdk1/2/4
inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.
Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.</description><identifier>ISSN: 2041-1723</identifier><identifier>EISSN: 2041-1723</identifier><identifier>DOI: 10.1038/s41467-022-31332-1</identifier><identifier>PMID: 35739121</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38 ; 38/1 ; 38/15 ; 38/91 ; 631/250/232/2059 ; 631/532/1360 ; 631/532/1542 ; 631/80/641/2350 ; 64/60 ; Animals ; Cell Cycle ; Cell Differentiation - genetics ; Gene Expression Regulation ; Granulocytes - metabolism ; Humanities and Social Sciences ; Mammals - metabolism ; multidisciplinary ; Science ; Science (multidisciplinary) ; Transcription Factors - genetics ; Transcription Factors - metabolism</subject><ispartof>Nature communications, 2022-06, Vol.13 (1), p.3595-3595, Article 3595</ispartof><rights>The Author(s) 2022</rights><rights>2022. The Author(s).</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c283t-690c6d4d84e5d8a84d8dc02defd25ffe33d54638c0d53ec2f97406a8cda281ff3</cites><orcidid>0000-0002-3117-7832 ; 0000-0003-3743-0023 ; 0000-0001-8529-2740 ; 0000-0001-6391-625X ; 0000-0002-5884-3380 ; 0000-0001-7446-9918 ; 0000-0001-6043-0844 ; 0000-0002-4239-4939</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225994/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225994/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35739121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Theilgaard-Mönch, Kim</creatorcontrib><creatorcontrib>Pundhir, Sachin</creatorcontrib><creatorcontrib>Reckzeh, Kristian</creatorcontrib><creatorcontrib>Su, Jinyu</creatorcontrib><creatorcontrib>Tapia, Marta</creatorcontrib><creatorcontrib>Furtwängler, Benjamin</creatorcontrib><creatorcontrib>Jendholm, Johan</creatorcontrib><creatorcontrib>Jakobsen, Janus Schou</creatorcontrib><creatorcontrib>Hasemann, Marie Sigurd</creatorcontrib><creatorcontrib>Knudsen, Kasper Jermiin</creatorcontrib><creatorcontrib>Cowland, Jack Bernard</creatorcontrib><creatorcontrib>Fossum, Anna</creatorcontrib><creatorcontrib>Schoof, Erwin</creatorcontrib><creatorcontrib>Schuster, Mikkel Bruhn</creatorcontrib><creatorcontrib>Porse, Bo T.</creatorcontrib><title>Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation: In memoriam Professor Niels Borregaard</title><title>Nature communications</title><addtitle>Nat Commun</addtitle><addtitle>Nat Commun</addtitle><description>Differentiation of multipotent stem cells into mature cells is fundamental for development and homeostasis of mammalian tissues, and requires the coordinated induction of lineage-specific transcriptional programs and cell cycle withdrawal. To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of
Cdk1/2/4
inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.
Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.</description><subject>38</subject><subject>38/1</subject><subject>38/15</subject><subject>38/91</subject><subject>631/250/232/2059</subject><subject>631/532/1360</subject><subject>631/532/1542</subject><subject>631/80/641/2350</subject><subject>64/60</subject><subject>Animals</subject><subject>Cell Cycle</subject><subject>Cell Differentiation - genetics</subject><subject>Gene Expression Regulation</subject><subject>Granulocytes - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Mammals - metabolism</subject><subject>multidisciplinary</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>2041-1723</issn><issn>2041-1723</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kT1vFDEQhi0EIlHIH6BALmkM_to9b4OEIj4iRaIJtWXs8THRnr3Yuyeu5J_Hdxui0ODGI80774zeh5DXgr8TXJn3VQvdbxiXkimhlGTiGTmXXAsmNlI9f1Kfkcta73h7ahBG65fkTHWbVktxTv7cFpeqLzjNmBONzs-5sFBwD4n6nEvA5E6tHKmHcaT-4Eeg8Btn6lKgIyZwW2B1Ao8R_SrGRPe4zzQsBdOWbtuSZcz-MKOnAWOEAmnGk_YVeRHdWOHy4b8g3z9_ur36ym6-fbm--njDvDRqZv3AfR90MBq6YJxpVfBcBohBds1QqdDpXhnPQ6fAyzhsNO-d8cFJI2JUF-TD6jstP3YQfDuguNFOBXeuHGx2aP_tJPxpt3lvBym7YdDN4O2DQcm_Fqiz3WE9RuIS5KVa2ZtGZhi4alK5Sn3JtRaIj2sEt0d8dsVnGz57wmdFG3rz9MDHkb-wmkCtgjodU4Vi7_JSUgvtf7b3sKuq6g</recordid><startdate>20220623</startdate><enddate>20220623</enddate><creator>Theilgaard-Mönch, Kim</creator><creator>Pundhir, Sachin</creator><creator>Reckzeh, Kristian</creator><creator>Su, Jinyu</creator><creator>Tapia, Marta</creator><creator>Furtwängler, Benjamin</creator><creator>Jendholm, Johan</creator><creator>Jakobsen, Janus Schou</creator><creator>Hasemann, Marie Sigurd</creator><creator>Knudsen, Kasper Jermiin</creator><creator>Cowland, Jack Bernard</creator><creator>Fossum, Anna</creator><creator>Schoof, Erwin</creator><creator>Schuster, Mikkel Bruhn</creator><creator>Porse, Bo T.</creator><general>Nature Publishing Group UK</general><scope>C6C</scope><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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3117-7832</orcidid><orcidid>https://orcid.org/0000-0003-3743-0023</orcidid><orcidid>https://orcid.org/0000-0001-8529-2740</orcidid><orcidid>https://orcid.org/0000-0001-6391-625X</orcidid><orcidid>https://orcid.org/0000-0002-5884-3380</orcidid><orcidid>https://orcid.org/0000-0001-7446-9918</orcidid><orcidid>https://orcid.org/0000-0001-6043-0844</orcidid><orcidid>https://orcid.org/0000-0002-4239-4939</orcidid></search><sort><creationdate>20220623</creationdate><title>Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation</title><author>Theilgaard-Mönch, Kim ; 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To understand the underlying regulatory mechanisms of this fundamental process, we investigated how the tissue-specific transcription factors, CEBPA and CEBPE, coordinate cell cycle exit and lineage-specification in vivo during granulocytic differentiation. We demonstrate that CEBPA promotes lineage-specification by launching an enhancer-primed differentiation program and direct activation of CEBPE expression. Subsequently, CEBPE confers promoter-driven cell cycle exit by sequential repression of MYC target gene expression at the G1/S transition and E2F-meditated G2/M gene expression, as well as by the up-regulation of
Cdk1/2/4
inhibitors. Following cell cycle exit, CEBPE unleashes the CEBPA-primed differentiation program to generate mature granulocytes. These findings highlight how tissue-specific transcription factors coordinate cell cycle exit with differentiation through the use of distinct gene regulatory elements.
Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>35739121</pmid><doi>10.1038/s41467-022-31332-1</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3117-7832</orcidid><orcidid>https://orcid.org/0000-0003-3743-0023</orcidid><orcidid>https://orcid.org/0000-0001-8529-2740</orcidid><orcidid>https://orcid.org/0000-0001-6391-625X</orcidid><orcidid>https://orcid.org/0000-0002-5884-3380</orcidid><orcidid>https://orcid.org/0000-0001-7446-9918</orcidid><orcidid>https://orcid.org/0000-0001-6043-0844</orcidid><orcidid>https://orcid.org/0000-0002-4239-4939</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 38 38/1 38/15 38/91 631/250/232/2059 631/532/1360 631/532/1542 631/80/641/2350 64/60 Animals Cell Cycle Cell Differentiation - genetics Gene Expression Regulation Granulocytes - metabolism Humanities and Social Sciences Mammals - metabolism multidisciplinary Science Science (multidisciplinary) Transcription Factors - genetics Transcription Factors - metabolism |
title | Transcription factor-driven coordination of cell cycle exit and lineage-specification in vivo during granulocytic differentiation: In memoriam Professor Niels Borregaard |
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