| Literature DB >> 33504783 |
Arthur Flohr Svendsen1, Jasper Panten2,3,4, Nicolas Rama5, Simon Renders2,3,6, Maria Maryanovich7,8,9, Pia Sommerkamp2,3,4, Luisa Ladel2,3, Anna Rita Redavid5, Benjamin Gibert5, Seka Lazare1, Benjamin Ducarouge5, Katharina Schönberger10, Andreas Narr2,3,4, Manon Tourbez1, Bertien Dethmers-Ausema1, Erik Zwart1, Agnes Hotz-Wagenblatt11, Dachuan Zhang7,8,9, Claudia Korn12,13,14, Petra Zeisberger2,3, Adriana Przybylla2,3, Markus Sohn2,3, Simon Mendez-Ferrer12,13,14, Mathias Heikenwälder15, Maik Brune16, Daniel Klimmeck2,3, Leonid Bystrykh1, Paul S Frenette7,8,9, Patrick Mehlen5, Gerald de Haan1, Nina Cabezas-Wallscheid17, Andreas Trumpp18,19,20.
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.Entities:
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Year: 2021 PMID： 33504783 PMCID： PMC7840807 DOI： 10.1038/s41467-020-20801-0
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919