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

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 e...

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Bibliographic Details
Published in:Nature communications 2021-07, Vol.12 (1), p.4484-4484, Article 4484
Main Authors: Cacialli, Pietro, Mahony, Christopher B., Petzold, Tim, Bordignon, Patrizia, Rougemont, Anne-Laure, Bertrand, Julien Y.
Format: Article
Language:English
Subjects:
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Antioxidants
Byproducts
Cells (biology)
Danio rerio
Detoxification
Embryogenesis
Embryonic growth stage
Endothelium
Fetuses
Glutathione
Hematopoietic stem cells
Humanities and Social Sciences
Immune response
Liver
Mammals
Molecular modelling
multidisciplinary
Niches
Oxidative stress
Progenitor cells
Reactive oxygen species
Science
Science (multidisciplinary)
Stems
Zebrafish
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Summary: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. Reactive oxygen species (ROS) are metabolic by-products which in excess can be toxic for hematopoietic stem and progenitor cells (HSPCs). Here the authors show that toxic ROS are transferred by expanding HSPCs to the zebrafish developmental niche via connexin Cx41.8 , where Ifi30 promotes their detoxification.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-24831-0