Connexin 41.8 governs timely haematopoietic stem and progenitor cell specification

Article Article scientifique Article Connexin 41.8 governs timely haematopoietic stem and progenitor cell specification eng 2025-08-12 2025-08-15 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.,Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.,DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany. 931376 author Brivio Sarah 0000-0003-1913-8686 University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland. 986295 Département de pathologie et immunologie (PATIM) author Linnerz Tanja 0000-0001-8127-780X University of Geneva, Faculty of Medicine, Department of Pathology and Immunology, Rue Michel-Servet 1, Geneva 4, Switzerland.,University of Auckland, Faculty of Medical and Health Sciences, Department of Molecular Medicine and Pathology, 85 Park Road, 1023 Auckland, New Zealand. 812915 author Watanabe Masakatsu 0000-0002-5744-197X Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan. author Gerhardt Holger 0000-0002-3030-0384 Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.,DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.,Charité - Universitätsmedizin Berlin, Berlin, Germany. 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) bio062118 10.1242/bio.062118 40605752 2046-6390 PMC12381925 https://journals.biologists.com/bio/article/14/8/bio062118/368872/Connexin-41-8-governs-timely-haematopoietic-stem Haematopoietic stem and progenitor cells (HSPCs) derive from a subset of endothelial cells (ECs), known as haemogenic ECs by the process of endothelial-to-haematopoietic transition (EHT). Although many factors involved in EHT have been elucidated, we still have a poor understanding of the temporal regulation of this process. Mitochondrial-derived reactive oxygen species (ROS) have been shown to stabilise the hypoxia-inducible factor 1/2α (Hif1/2α) proteins, allowing them to positively regulate EHT. Here, we show a developmental delay in EHT and HSPC induction in a connexin (cx)41.8 (orthologous to mammalian CX40) gap junction mutant, in zebrafish. In mammalian cells, CX40 has been shown to localise to the mitochondria. We demonstrate that Cx41.8 is important for the correct temporal generation of mitochondrial ROS, which stabilise the Hif pathway, allowing for the subsequent specification of the haemogenic endothelium. Taken together, our data indicate that Cx41.8 governs the correct temporal induction of HSPCs. CX40 Cx41.8 HSPC ROS Zebrafish Dewey 616.07 Fondation Privée des Hopitaux de Genève RC05-03 Swiss National Science Foundation Hematopoietic Stem Cells and their niche: origin and maturation during embryonic development 184814 CH Projects 137 Département de pathologie et immunologie 21F false 577 Développement du système hémato-vasculaire chez les vertébrés 920 https://yareta.unige.ch/archives/74e35492-529f-4266-a898-4f43dc5e6102 Biology open 14 8 ec1762e4-15d8-415c-9f10-af9e359bb9ca Article (Published version) Public bio062118.pdf 9085404 application/pdf CC BY-4.0 e8b851fed0673c148ab625d4974e1661dc8c7cbf5f0d144bfebba0b973e1b2d0 f88ca9c4-ea9c-45c5-8db2-21b6e95558e1 Supplemental data Public bio062118supp.pdf 8684040 application/pdf f1c2552bd501d295d3786c8348071b8e6a10715379b1a1968b080e63156d4b3e openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Brivio, Sarah