A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress

Article Article scientifique Article A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress eng 2021 author Cacialli Pietro 866763 author Mahony Christopher 811138 author Petzold Tim 0000-0001-9788-6167 931376 author Bordignon Patrizia 858039 author Rougemont-Pidoux Anne-Laure 29140 author Bertrand Julien 0000-0001-6570-4082 778947 4484 10.1038/s41467-021-24831-0 34301940 2041-1723 Reactive oxygen species (ROS) represent a by-product of metabolism and their excess is toxic for hematopoietic stem and progenitor cells (HSPCs). During embryogenesis, a small number of HSPCs are produced from the hemogenic endothelium, before they colonize a transient organ where they expand, for example the fetal liver in mammals. In this study, we use zebrafish to understand the molecular mechanisms that are important in the caudal hematopoietic tissue (equivalent to the mammalian fetal liver) to promote HSPC expansion. High levels of ROS are deleterious for HSPCs in this niche, however this is rescued by addition of antioxidants. We show that Cx41.8 is important to lower ROS levels in HSPCs. We also demonstrate a new role for ifi30, known to be involved in the immune response. In the hematopoietic niche, Ifi30 can recycle oxidized glutathione to allow HSPCs to dampen their levels of ROS, a role that could be conserved in human fetal liver. Animals Genetically Modified Connexins/genetics/metabolism Embryo Nonmammalian/cytology/embryology/metabolism Gene Expression Regulation Developmental Hematopoietic Stem Cells/cytology/metabolism Humans Microscopy Confocal Mutation Oxidative Stress Oxidoreductases Acting on Sulfur Group Donors/genetics/metabolism Signal Transduction/genetics Stem Cell Niche Time-Lapse Imaging/methods Zebrafish/embryology/genetics Zebrafish Proteins/genetics/metabolism Dewey 616.07 Swiss National Science Foundation 31003_166515 CH Swiss National Science Foundation Hematopoietic Stem Cells and their niche: origin and maturation during embryonic development 310030_184814 CH Project funding 137 Département de pathologie et immunologie 21F false 577 Développement du système hémato-vasculaire chez les vertébrés 920 https://yareta.unige.ch/#/home/detail/d848eaf9-3970-44c6-a9aa-83424b0dc224 Nature Communications 12 1 92b736ab-b803-4f6f-95bc-6aa18f826d9f Article (Published version) Public 41467_2021_Article_24831.pdf 10170639 application/pdf CC BY b238d88a-46eb-4acd-aa05-7b624d7e9094 Supplemental data Public 41467_2021_24831_MOESM1_ESM-1.pdf 33665198 application/pdf CC BY 72716334-71c8-405d-9157-ec6cf8c4bf27 Supplemental data Public 41467_2021_24831_MOESM4_ESM-1.pdf 468877 application/pdf CC BY 3f2bf182-54a7-4e82-afb0-2cc8f5d8fe54 Supplemental data Public 41467_2021_24831_MOESM5_ESM.mp4 7154250 video/mp4 CC BY db4f4761-032e-437e-a252-8ff5e4fbdc89 Supplemental data Public 41467_2021_24831_MOESM6_ESM.mp4 6749688 video/mp4 CC BY 80992bb1-c0e5-4bc6-868a-ad90a995a33b Supplemental data Public 41467_2021_24831_MOESM7_ESM.mp4 16894680 video/mp4 CC BY 11f465e1-5c04-4008-a352-76e4198ea84b Supplemental data Public 41467_2021_24831_MOESM8_ESM.mp4 13827568 video/mp4 CC BY 77312482-9d95-46d4-aa44-2142131c6bc8 Supplemental data Public 41467_2021_24831_MOESM9_ESM.mp4 1837856 video/mp4 CC BY 8b9db412-fea4-47ce-ac61-1006b1d21b3b Supplemental data Public 41467_2021_24831_MOESM10_ESM.mp4 1824921 video/mp4 CC BY 7bdf43a1-38f8-4e60-b3c0-e41c56fa60db Supplemental data Public 41467_2021_24831_MOESM11_ESM.mp4 12675074 video/mp4 CC BY 006a7f61-e6a0-4a46-858a-fa6bc8f06d6b Supplemental data Public 41467_2021_24831_MOESM12_ESM.mp4 1846734 video/mp4 CC BY 74bdd30d-8750-4d17-96a5-b8e43cf89756 Supplemental data Public 41467_2021_24831_MOESM13_ESM.mp4 4619701 video/mp4 CC BY e9c30004-9c60-4581-bb01-86855b2ffc8d Supplemental data Public 41467_2021_24831_MOESM14_ESM.mp4 5328780 video/mp4 CC BY openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress	Nature Communications			2021	338	337

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Bordignon, Patrizia