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

Research output: Contribution to journalArticlepeer-review

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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 languageEnglish
Article number4484
Number of pages15
JournalNature Communications
Volume12
Issue number1
Early online date23 Jul 2021
DOIs
Publication statusPublished - 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

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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