Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2021

Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1

Erik Zwart
Leonid Bystrykh
Gerald de Haan

Résumé

Abstract Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential associated to dormancy. Here we identify the cell surface receptor neogenin-1 as specifically expressed in dormant HSCs. Loss of neogenin-1 initially leads to increased HSC expansion but subsequently to loss of self-renewal and premature exhaustion in vivo. Its ligand netrin-1 induces Egr1 expression and maintains quiescence and function of cultured HSCs in a Neo1 dependent manner. Produced by arteriolar endothelial and periarteriolar stromal cells, conditional netrin-1 deletion in the bone marrow niche reduces HSC numbers, quiescence and self-renewal, while overexpression increases quiescence in vivo. Ageing associated bone marrow remodelling leads to the decline of netrin-1 expression in niches and a compensatory but reversible upregulation of neogenin-1 on HSCs. Our study suggests that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1 function. Decline of netrin-1 production during ageing leads to the gradual decrease of Neo1 mediated HSC self-renewal.
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Dates et versions

hal-03428982 , version 1 (15-11-2021)

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Simon Renders, Arthur Flohr Svendsen, Jasper Panten, Nicolas Rama, Maria Maryanovich, et al.. Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1. Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-020-20801-0⟩. ⟨hal-03428982⟩
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