PUBLICATION
A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress
- Authors
- Cacialli, P., Mahony, C.B., Petzold, T., Bordignon, P., Rougemont, A.L., Bertrand, J.Y.
- ID
- ZDB-PUB-210728-14
- Date
- 2021
- Source
- Nature communications 12: 4484 (Journal)
- Registered Authors
- Bertrand, Julien, Cacialli, Pietro, Mahony, Christopher
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Connexins/genetics*
- Connexins/metabolism
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/embryology
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental
- Hematopoietic Stem Cells/cytology
- Hematopoietic Stem Cells/metabolism*
- Humans
- Microscopy, Confocal
- Mutation
- Oxidative Stress*
- Oxidoreductases Acting on Sulfur Group Donors/genetics*
- Oxidoreductases Acting on Sulfur Group Donors/metabolism
- Signal Transduction/genetics*
- Stem Cell Niche*
- Time-Lapse Imaging/methods
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 34301940 Full text @ Nat. Commun.
Citation
Cacialli, P., Mahony, C.B., Petzold, T., Bordignon, P., Rougemont, A.L., Bertrand, J.Y. (2021) A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress. Nature communications. 12:4484.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping