Contributors: Lymphocytes et Immunité - Lymphocytes and Immunity; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Cellule Pasteur; Sorbonne Université (SU); Macrophages et Cellules endothéliales / Macrophages and Endothelial Cells; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); University of Rochester Medical Center (URMC); Kyushu University; This work was supported by the Institut Pasteur, Institut National de la Santé etde la Recherche Médicale, Agence Nationale de la Recherche (grantTwothyme, grant EPI-DEV and grant DELSTAR), REVIVE Future InvestmentProgram and Ligue Nationale contre le Cancer through grants to A. Cumano.F.S.S. was financed by a postdoctoral grant from REVIVE (ANR-10-LABX-73).G. Nogueira was financed by a doctoral grant from REVIVE (ANR-10-LABX-73). This work was also funded by Revive (Investissement d’avenir; ANR-10-LABX-0073) and the European Research Council ERC investigator award(2016-StG-715320 to E.G.P.). R.E. was funded by a postdoctoral grant fromREVIVE (ANR-10-LABX-73).; We acknowledge the Center for Translational Science (CRT) - Cytometry and Biomarkers Unit of Technology and Service (CB UTechS) at Institut Pasteur for support in conducting this study, namely S. Novault, S. Megharba, S. Schmutz; and the staff of the animal facility of the Institut Pasteur for mouse care.; ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010); ANR-14-CE11-0022,Twothyme,Deux progéniteurs hématopoïétiques différents établissent le compartiment de lymphocytes T: tester un nouveau paradigme du développement T.(2014); ANR-19-CE14-0018,Epi-Dev,Bases moléculaires de la spécification vers le lignage lymphoïde : une approche comparative trans-espèce(2019); ANR-21-CE15-0028,DELSTAR,Développement des cellules lymphoïdes embryonnaires qui organisent l'architecture du thymus(2021); European Project: 715320,ERC-2016-STG,ResidentMacroPhage(2016)
Abstract: It was proposed that two sequential sources of intraembryonic multipotent progenitors ensure blood cell production from late gestation into adulthood, with only the latter producing self-renewing hematopoietic stem cells (HSC). How these two populations differ and how they impact the establishment of the postnatal immune system, remains poorly understood. Using complementary lineage tracing models, we showed that the first emerging embryonic multipotent progenitors (eMPP) are responsible for late gestation hematopoiesis. They are distinct from HSC that do not significantly contribute to embryonic mature blood cells. eMPP are the predominant source of embryonic lymphocytes and lymphoid tissue inducer cells, some of which persist for life. Between E12.5 and E16.5 eMPP rapidly differentiate, whereas HSC expand 20fold. Altogether, these results support the notion that eMPP establish the embryonic adaptive immune system and shape the lymphoid organs where later adaptive immune responses occur, while HSC expand to sustain blood cell production throughout life. .
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