Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9.sup.High Committed Megakaryocytic Progenitors
This study aimed at reinvestigating the controversial contribution of Notch signaling to megakaryocytic lineage development. For that purpose, we combined colony assays and single cells progeny analyses of purified megakaryocyte-erythroid progenitors (MEP) after short-term cultures on recombinant No...
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description | This study aimed at reinvestigating the controversial contribution of Notch signaling to megakaryocytic lineage development. For that purpose, we combined colony assays and single cells progeny analyses of purified megakaryocyte-erythroid progenitors (MEP) after short-term cultures on recombinant Notch ligand rDLL1. We showed that Notch activation stimulated the SCF-dependent and preferential amplification of Kit.sup.+ erythroid and bipotent progenitors while favoring commitment towards the erythroid at the expense of megakaryocytic lineage. Interestingly, we also identified a CD9.sup.High MEP subset that spontaneously generated almost exclusively megakaryocytic progeny mainly composed of single megakaryocytes. We showed that Notch activation decreased the extent of polyploidization and maturation of megakaryocytes, increased the size of megakaryocytic colonies and surprisingly restored the generation of erythroid and mixed colonies by this CD9.sup.High MEP subset. Importantly, the size increase of megakaryocytic colonies occurred at the expense of the production of single megakaryocytes and the restoration of colonies of alternative lineages occurred at the expense of the whole megakaryocytic progeny. Altogether, these results indicate that Notch activation is able to extend the number of divisions of MK-committed CD9.sup.High MEPs before terminal maturation while allowing a fraction of them to generate alternative lineages. This unexpected plasticity of MK-committed progenitors revealed upon Notch activation helps to better understand the functional promiscuity between megakaryocytic lineage and hematopoietic stem cells. |
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For that purpose, we combined colony assays and single cells progeny analyses of purified megakaryocyte-erythroid progenitors (MEP) after short-term cultures on recombinant Notch ligand rDLL1. We showed that Notch activation stimulated the SCF-dependent and preferential amplification of Kit.sup.+ erythroid and bipotent progenitors while favoring commitment towards the erythroid at the expense of megakaryocytic lineage. Interestingly, we also identified a CD9.sup.High MEP subset that spontaneously generated almost exclusively megakaryocytic progeny mainly composed of single megakaryocytes. We showed that Notch activation decreased the extent of polyploidization and maturation of megakaryocytes, increased the size of megakaryocytic colonies and surprisingly restored the generation of erythroid and mixed colonies by this CD9.sup.High MEP subset. Importantly, the size increase of megakaryocytic colonies occurred at the expense of the production of single megakaryocytes and the restoration of colonies of alternative lineages occurred at the expense of the whole megakaryocytic progeny. Altogether, these results indicate that Notch activation is able to extend the number of divisions of MK-committed CD9.sup.High MEPs before terminal maturation while allowing a fraction of them to generate alternative lineages. This unexpected plasticity of MK-committed progenitors revealed upon Notch activation helps to better understand the functional promiscuity between megakaryocytic lineage and hematopoietic stem cells.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0153860</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Analysis ; Bone marrow cells ; Cell differentiation ; Cell proliferation ; Hematopoietic stem cells</subject><ispartof>PloS one, 2016-04, Vol.11 (4)</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids></links><search><creatorcontrib>Weiss-Gayet, Michèle</creatorcontrib><creatorcontrib>Starck, Joëlle</creatorcontrib><creatorcontrib>Chaabouni, Azza</creatorcontrib><creatorcontrib>Chazaud, Bénédicte</creatorcontrib><creatorcontrib>Morlé, François</creatorcontrib><title>Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9.sup.High Committed Megakaryocytic Progenitors</title><title>PloS one</title><description>This study aimed at reinvestigating the controversial contribution of Notch signaling to megakaryocytic lineage development. For that purpose, we combined colony assays and single cells progeny analyses of purified megakaryocyte-erythroid progenitors (MEP) after short-term cultures on recombinant Notch ligand rDLL1. We showed that Notch activation stimulated the SCF-dependent and preferential amplification of Kit.sup.+ erythroid and bipotent progenitors while favoring commitment towards the erythroid at the expense of megakaryocytic lineage. Interestingly, we also identified a CD9.sup.High MEP subset that spontaneously generated almost exclusively megakaryocytic progeny mainly composed of single megakaryocytes. We showed that Notch activation decreased the extent of polyploidization and maturation of megakaryocytes, increased the size of megakaryocytic colonies and surprisingly restored the generation of erythroid and mixed colonies by this CD9.sup.High MEP subset. Importantly, the size increase of megakaryocytic colonies occurred at the expense of the production of single megakaryocytes and the restoration of colonies of alternative lineages occurred at the expense of the whole megakaryocytic progeny. Altogether, these results indicate that Notch activation is able to extend the number of divisions of MK-committed CD9.sup.High MEPs before terminal maturation while allowing a fraction of them to generate alternative lineages. This unexpected plasticity of MK-committed progenitors revealed upon Notch activation helps to better understand the functional promiscuity between megakaryocytic lineage and hematopoietic stem cells.</description><subject>Analysis</subject><subject>Bone marrow cells</subject><subject>Cell differentiation</subject><subject>Cell proliferation</subject><subject>Hematopoietic stem cells</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqN0M9LwzAUB_AiCur0P_AQEAQPrenStd1xzh8TNidOvY7X9KXLTJPRpOiO_ufGH4cNPEgO773w-T5IguAkplHMsvhiadpGg4pWRmNE4x7LU7oTHMR91g3TLmW7G_1-cGjtktIvlB4EH_fG8QWZOVm3Chxacmmcn1GJ8BE1voEioEsylhqhQvKgwDrJpVsTqQmQWVtYdMQIMmkbb8jwqh_ZdhWNZLUgQ1PX0jksyQQreIVmbfjax8lDYyrU0pnGHgV7ApTF49_aCZ5vrp-Go3A8vb0bDsZhFacpC4usRxFpkiWZYJxTUfpJdPM8TvqMZSIvk7xIEYqkx8suIgMBlBc05qzwj2esE5z-7K1A4VxqYVwDvJaWzwdJjyVJTr9V9Ifyp8Racv-_Qvr7rcD5VsAbh--ugtba-d3s8f92-rJtzzbsAkG5hTWqddJouwk_ATPYnao</recordid><startdate>20160418</startdate><enddate>20160418</enddate><creator>Weiss-Gayet, Michèle</creator><creator>Starck, Joëlle</creator><creator>Chaabouni, Azza</creator><creator>Chazaud, Bénédicte</creator><creator>Morlé, François</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20160418</creationdate><title>Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9.sup.High Committed Megakaryocytic Progenitors</title><author>Weiss-Gayet, Michèle ; Starck, Joëlle ; Chaabouni, Azza ; Chazaud, Bénédicte ; Morlé, François</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1663-b750ee04747f3cc0fdee0f288149337f8d48b6eab45cd2ee3afa0cb01c3b19333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Analysis</topic><topic>Bone marrow cells</topic><topic>Cell differentiation</topic><topic>Cell proliferation</topic><topic>Hematopoietic stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weiss-Gayet, Michèle</creatorcontrib><creatorcontrib>Starck, Joëlle</creatorcontrib><creatorcontrib>Chaabouni, Azza</creatorcontrib><creatorcontrib>Chazaud, Bénédicte</creatorcontrib><creatorcontrib>Morlé, François</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weiss-Gayet, Michèle</au><au>Starck, Joëlle</au><au>Chaabouni, Azza</au><au>Chazaud, Bénédicte</au><au>Morlé, François</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9.sup.High Committed Megakaryocytic Progenitors</atitle><jtitle>PloS one</jtitle><date>2016-04-18</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This study aimed at reinvestigating the controversial contribution of Notch signaling to megakaryocytic lineage development. For that purpose, we combined colony assays and single cells progeny analyses of purified megakaryocyte-erythroid progenitors (MEP) after short-term cultures on recombinant Notch ligand rDLL1. We showed that Notch activation stimulated the SCF-dependent and preferential amplification of Kit.sup.+ erythroid and bipotent progenitors while favoring commitment towards the erythroid at the expense of megakaryocytic lineage. Interestingly, we also identified a CD9.sup.High MEP subset that spontaneously generated almost exclusively megakaryocytic progeny mainly composed of single megakaryocytes. We showed that Notch activation decreased the extent of polyploidization and maturation of megakaryocytes, increased the size of megakaryocytic colonies and surprisingly restored the generation of erythroid and mixed colonies by this CD9.sup.High MEP subset. Importantly, the size increase of megakaryocytic colonies occurred at the expense of the production of single megakaryocytes and the restoration of colonies of alternative lineages occurred at the expense of the whole megakaryocytic progeny. Altogether, these results indicate that Notch activation is able to extend the number of divisions of MK-committed CD9.sup.High MEPs before terminal maturation while allowing a fraction of them to generate alternative lineages. This unexpected plasticity of MK-committed progenitors revealed upon Notch activation helps to better understand the functional promiscuity between megakaryocytic lineage and hematopoietic stem cells.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0153860</doi></addata></record> |
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source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Analysis Bone marrow cells Cell differentiation Cell proliferation Hematopoietic stem cells |
title | Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9.sup.High Committed Megakaryocytic Progenitors |
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