Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1
Authors
Renders, Simon
Svendsen, Arthur Flohr
Panten, Jasper
Sommerkamp, Pia
Ladel, Luisa
Redavid, Anna Rita
Lazare, Seka
Ducarouge, Benjamin
Schönberger, Katharina
Narr, Andreas
Tourbez, Manon
Dethmers-Ausema, Bertien
Hotz-Wagenblatt, Agnes
Korn, Claudia
Zeisberger, Petra
Przybylla, Adriana
Sohn, Markus
Brune, Maik
Klimmeck, Daniel
Mehlen, Patrick
Publication Date
2021-01-27Journal Title
Nature Communications
Publisher
Nature Publishing Group UK
Volume
12
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Renders, S., Svendsen, A. F., Panten, J., Rama, N., Maryanovich, M., Sommerkamp, P., Ladel, L., et al. (2021). Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1. Nature Communications, 12 (1) https://doi.org/10.1038/s41467-020-20801-0
Description
Funder: Studienstiftung des Deutschen Volkes (German National Academic Foundation); doi: https://doi.org/10.13039/501100004350
Funder: Heinrich F.C. Behr Stiftung
Funder: Dietmar Hopp Stiftung; doi: https://doi.org/10.13039/501100005941
Abstract
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.
Keywords
Article, /631/443/7, /631/532/1542, /631/532/2441, /631/532/2139, /13/31, /38/91, /13/51, /13/100, /13/106, /14/19, /64/60, article
Sponsorship
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) (ERC-Stg-2017)
Deutsche Forschungsgemeinschaft (German Research Foundation) (FOR2033, SFB873)
Identifiers
s41467-020-20801-0, 20801
External DOI: https://doi.org/10.1038/s41467-020-20801-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/316773
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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