Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1.
Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1.
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DOI：
10.1038/s41467-020-20801-0
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发表时间：
2021-01-27
影响因子：
16.6
通讯作者：
Trumpp A
中科院分区：
文献类型：
--
作者：
Renders S;Svendsen AF;Panten J;Rama N;Maryanovich M;Sommerkamp P;Ladel L;Redavid AR;Gibert B;Lazare S;Ducarouge B;Schönberger K;Narr A;Tourbez M;Dethmers-Ausema B;Zwart E;Hotz-Wagenblatt A;Zhang D;Korn C;Zeisberger P;Przybylla A;Sohn M;Mendez-Ferrer S;Heikenwälder M;Brune M;Klimmeck D;Bystrykh L;Frenette PS;Mehlen P;de Haan G;Cabezas-Wallscheid N;Trumpp A
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. Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential and associated dormancy. Here the authors show that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1, and that decline of netrin-1 production during ageing leads to decreased Neo1 mediated HSC self-renewal.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.5
作者：
Bernitz, Jeffrey M.;Kim, Huen Suk;MacArthur, Ben;Sieburg, Hans;Moore, Kateri
通讯作者：
Moore, Kateri
影响因子：
21.3
作者：
Asada N;Kunisaki Y;Pierce H;Wang Z;Fernandez NF;Birbrair A;Ma'ayan A;Frenette PS
通讯作者：
Frenette PS
影响因子：
30.5
作者：
Duchene J;Novitzky-Basso I;Thiriot A;Casanova-Acebes M;Bianchini M;Etheridge SL;Hub E;Nitz K;Artinger K;Eller K;Caamaño J;Rülicke T;Moss P;Megens RTA;von Andrian UH;Hidalgo A;Weber C;Rot A
通讯作者：
Rot A
影响因子：
23.9
作者：
Florian, Maria Carolina;Doerr, Karin;Niebel, Anja;Daria, Deidre;Schrezenmeier, Hubert;Rojewski, Markus;Filippi, Marie-Dominique;Hasenberg, Anja;Gunzer, Matthias;Scharffetter-Kochanek, Karin;Zheng, Yi;Geiger, Hartmut
通讯作者：
Geiger, Hartmut