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

Pietro Cacialli; Christopher B. Mahony; Tim Petzold; Patrizia Bordignon; Anne Laure Rougemont; Julien Y. Bertrand

doi:10.1038/s41467-021-24831-0

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

Pietro Cacialli, Christopher B. Mahony, Tim Petzold, Patrizia Bordignon, Anne Laure Rougemont, Julien Y. Bertrand^*

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	4484
Number of pages	15
Journal	Nature Communications
Volume	12
Issue number	1
Early online date	23 Jul 2021
DOIs	https://doi.org/10.1038/s41467-021-24831-0
Publication status	Published - Dec 2021

Bibliographical note

Funding Information:
We would like to thank all lab members for their comments. We would also like to thank Pr. B. Kwak for sharing her expertise on connexins, and N. Liaudet from the Bioimaging platform for his help with the Imaris software. J.Y.B. was endorsed by a chair in life sciences funded by the Gabriella Giorgi-Cavaglieri Foundation and is also funded by the Swiss National Fund (grants #31003_166515 and 310030_184814).

Publisher Copyright:
© 2021, The Author(s).

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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CacialliP2021connexinFinal published version, 9.7 MBLicence: Creative Commons: Attribution (CC BY)

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title = "A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress",

abstract = "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.",

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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