title: Notch Stimulates Both Self-Renewal and Lineage Plasticity in a Subset of Murine CD9High Committed Megakaryocytic Progenitors.
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+ erythroid and bipotent progenitors while favoring commitment towards the erythroid at the expense of megakaryocytic lineage. Interestingly, we also identified a CD9High 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 CD9High 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 CD9High 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.
authors.affiliation: Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon1, Villeurbanne, France.|INSERM U1217, Villeurbanne, France.|CNRS UMR 5310, Villeurbanne, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Weiss-Gayet
authors.affiliation: Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon1, Villeurbanne, France.|INSERM U1217, Villeurbanne, France.|CNRS UMR 5310, Villeurbanne, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Starck
authors.affiliation: Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon1, Villeurbanne, France.|INSERM U1217, Villeurbanne, France.|CNRS UMR 5310, Villeurbanne, France.
authors.forename: Azza
authors.initials: A
authors.lastname: Chaabouni
authors.affiliation: Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon1, Villeurbanne, France.|INSERM U1217, Villeurbanne, France.|CNRS UMR 5310, Villeurbanne, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
authors.affiliation: Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon1, Villeurbanne, France.|INSERM U1217, Villeurbanne, France.|CNRS UMR 5310, Villeurbanne, France.
authors.forename: François
authors.initials: F
authors.lastname: Morlé
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060245:Tetraspanin 29 / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; C554870:Cd9 protein, mouse; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; D060245:Tetraspanin 29