BMAL1 modulates glutamine supply to control haematopoietic stem and progenitor cell expansion

Article Article scientifique Article BMAL1 modulates glutamine supply to control haematopoietic stem and progenitor cell expansion eng 2026-04-14 2026-04-15 author Petzold Tim 0000-0001-9788-6167 University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland.,Integrative Vascular Biology Laboratory, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.,DZHK (German Center for Cardiovascular Research), 10785 Berlin, Germany. 931376 author Lutes Lydia Kay 0000-0001-6133-6294 University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland. 948114 author Navarro I Batista Keila 0009-0003-0542-6983 University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland. 940238 author Konle Antonia Integrative Vascular Biology Laboratory, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. author Baechler Bastien University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland. 843251 Département de pathologie et immunologie (PATIM) author Jemelin Stéphane University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland. 116782 Département de pathologie et immunologie (PATIM) author Gerhardt Holger 0000-0002-3030-0384 Integrative Vascular Biology Laboratory, Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.,DZHK (German Center for Cardiovascular Research), 10785 Berlin, Germany.,Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany. author Golub Rachel 0000-0002-2306-5363 Institut Pasteur, Université Paris Cité, INSERM U1223, Lymphocyte and Immunity Unit, 75015 Paris, France. author Scheiermann Christoph 0000-0002-9212-0995 University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland.,Biomedical Center (BMC), Institute for Cardiovascular Physiology and Pathophysiology, Walter Brendel Center for Experimental Medicine (WBex), Faculty of Medicine, Ludwig-Maximilians-Universität (LMU) Munich, Planegg-Martinsried, 82152 Munich, Germany.,Geneva Centre of Inflammation Research, University of Geneva, Faculty of Medicine, Rue Michel-Servet 1, Geneva 4, Switzerland. 891044 Département de pathologie et immunologie (PATIM) author Bertrand Julien 0000-0001-6570-4082 University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland.,Geneva Centre of Inflammation Research, University of Geneva, Faculty of Medicine, Rue Michel-Servet 1, Geneva 4, Switzerland. 778947 Département de pathologie et immunologie (PATIM) dev204726 10.1242/dev.204726 41853934 0950-1991 PMC13120679 https://journals.biologists.com/dev/article/153/8/dev204726/371338/BMAL1-modulates-glutamine-supply-to-control Following specification in the dorsal aorta, haematopoietic stem and progenitor cells (HSPCs) proliferate in the HSPC niche, known as the caudal haematopoietic tissue (CHT) in zebrafish. Here, we demonstrate that bmal1a, a core component of the circadian clock machinery, is expressed in CHT endothelial cells (ECs) and affects HSPCs in a non-cell autonomous manner. Using endothelial cell-specific dominant-negative Bmal1a zebrafish lines, we demonstrate a striking increase in HSPC numbers in the CHT, resulting from enhanced HSPC proliferation. RNA-sequencing of dominant-negative bmal1a ECs sorted from the CHT shows a downregulation of glud1a, resulting in increased glutamine levels in the CHT. This newly discovered bmal1a-glud1a-glutamine pathway fuels HSPC expansion. We demonstrate that this glutamine synthesis pathway controlling HSPC expansion is likely conserved in the mouse fetal liver (FL) niche, in which hepatocytes are the likely source of glutamine. Together, our data uncover a previously unreported mechanism of HSPC homeostasis, in which EC BMAL1, expressed by the niche, controls the amount of bioavailable glutamine for HSPCs by regulating the expression of genes involved in glutamine synthesis. Endothelial cell Expansion Glutamine HSPC Mouse Niche Zebrafish Animals Glutamine / metabolism Zebrafish / metabolism Zebrafish / embryology ARNTL Transcription Factors / metabolism ARNTL Transcription Factors / genetics Hematopoietic Stem Cells / metabolism Hematopoietic Stem Cells / cytology Cell Proliferation Zebrafish Proteins / metabolism Zebrafish Proteins / genetics Mice Endothelial Cells / metabolism Endothelial Cells / cytology Gene Expression Regulation, Developmental Stem Cell Niche Liver / metabolism Liver / embryology Dewey 616.07 Deutsche Forschungsgemeinschaft TRR359 (491676693) Krebsliga Schweiz KLS-4836-08-2019 Ligue Genevoise Contre le Cancer 2106 Fondation Privée des Hopitaux de Genève RC05-03 The Research Council of Norway Qualifying for professional careers - stipendiat videreført etter at hovedprosjektet (197743 Qualifying for Professional Careers) avsluttes 228027 NO European Commission Regulation and relevance of circadian leukocyte dynamics for skin immune homeostasis 101001233 CIRCADYN EU H2020 Swiss National Science Foundation Mechanisms governing rhythmicity in adaptive immune responses 182417 CH 137 Département de pathologie et immunologie 21F false 577 Développement du système hémato-vasculaire chez les vertébrés 920 1259 L'influence du rôle du cycle circadien sur l'immunité 995 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE282622 https://doi.org/10.26037/yareta:2l3zxli34zdd3pgeq4cst75q5u Development 153 8 b2952726-b915-4ade-9711-e9ee278874e7 Article (Published version) Public Article_scientifique_from_europePmc.pdf 9389685 application/pdf CC BY-4.0 1068ade3013e6390811886f1b5f966aa930eb9964516c150629c3b787e35fc01 676b793a-17eb-4996-ab36-0ceb6e95ecd4 Appendix Public develop-153-204726_review_history.pdf 1017420 application/pdf 1e27926f899daa67df701491e2069f2a7e9191201afc80150428ff155b62ccfd e05da515-5c8c-48a8-9f18-4d6a10c76e7a Appendix Public develop-153-204726-s1.pdf 21403976 application/pdf 20b58c2a4e9c226263a0b3e92555501ac5c7c91841a5d47c38d92ac8846297ff openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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