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

Animals Arterioles / metabolism Cell Differentiation Cell Proliferation Cellular Senescence Gene Deletion Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells / metabolism Membrane Proteins / metabolism Mice, Mutant Strains Mice, Transgenic Netrin-1 / metabolism Signal Transduction Stem Cell Niche

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
27 01 2021
Historique:
received: 07 09 2019
accepted: 14 12 2020
entrez: 28 1 2021
pubmed: 29 1 2021
medline: 4 2 2021
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-20801-0 PMID: 33504783 PMC: PMC7840807
pubmed: 33504783
doi: 10.1038/s41467-020-20801-0
pii: 10.1038/s41467-020-20801-0
pmc: PMC7840807
doi:

Substances chimiques

Membrane Proteins 0
neogenin 0
Netrin-1 158651-98-0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

608

Subventions

Organisme : Medical Research Council
ID : MC_PC_17230
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V005421/1
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK056638
Pays : United States

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Auteurs

Simon Renders (S)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.

Arthur Flohr Svendsen (AF)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Jasper Panten (J)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Nicolas Rama (N)

Apoptosis, Cancer and Development Laboratory, Equipe labellisée "La Ligue," LabEx DEVweCAN, Institut Convergence Rabelais, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon1, Centre Léon Bérard, 69008, Lyon, France.
ORCID: 0000-0003-1614-7755

Maria Maryanovich (M)

Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
ORCID: 0000-0002-2015-0538

Pia Sommerkamp (P)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Luisa Ladel (L)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.

Anna Rita Redavid (AR)

Apoptosis, Cancer and Development Laboratory, Equipe labellisée "La Ligue," LabEx DEVweCAN, Institut Convergence Rabelais, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon1, Centre Léon Bérard, 69008, Lyon, France.

Benjamin Gibert (B)

Apoptosis, Cancer and Development Laboratory, Equipe labellisée "La Ligue," LabEx DEVweCAN, Institut Convergence Rabelais, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon1, Centre Léon Bérard, 69008, Lyon, France.
ORCID: 0000-0002-5295-3124

Seka Lazare (S)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Benjamin Ducarouge (B)

Apoptosis, Cancer and Development Laboratory, Equipe labellisée "La Ligue," LabEx DEVweCAN, Institut Convergence Rabelais, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon1, Centre Léon Bérard, 69008, Lyon, France.

Katharina Schönberger (K)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg, Germany.

Andreas Narr (A)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.

Manon Tourbez (M)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Bertien Dethmers-Ausema (B)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Erik Zwart (E)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
ORCID: 0000-0002-4552-003X

Agnes Hotz-Wagenblatt (A)

Core Facility Omics IT and Data Management, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Dachuan Zhang (D)

Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
ORCID: 0000-0002-1746-275X

Claudia Korn (C)

Wellcome Trust/MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AH, UK.
Department of Haematology, University of Cambridge, Cambridge, CB2 0AH, UK.
NHS Blood and Transplant, Cambridge, CB2 0PT, UK.

Petra Zeisberger (P)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.

Adriana Przybylla (A)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.

Markus Sohn (M)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.

Simon Mendez-Ferrer (S)

Wellcome Trust/MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AH, UK.
Department of Haematology, University of Cambridge, Cambridge, CB2 0AH, UK.
NHS Blood and Transplant, Cambridge, CB2 0PT, UK.
ORCID: 0000-0002-9805-9988

Mathias Heikenwälder (M)

Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.
ORCID: 0000-0002-3135-2274

Maik Brune (M)

Department of Internal Medicine I and Clinical Chemistry, Heidelberg University Hospital, Heidelberg, Germany.

Daniel Klimmeck (D)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.

Leonid Bystrykh (L)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
ORCID: 0000-0001-6924-5602

Paul S Frenette (PS)

Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
ORCID: 0000-0003-0862-9922

Patrick Mehlen (P)

Apoptosis, Cancer and Development Laboratory, Equipe labellisée "La Ligue," LabEx DEVweCAN, Institut Convergence Rabelais, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon1, Centre Léon Bérard, 69008, Lyon, France.

Gerald de Haan (G)

Laboratory of Ageing Biology and Stem Cells, European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
ORCID: 0000-0001-9706-0138

Nina Cabezas-Wallscheid (N)

Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg, Germany. cabezas@ie-freiburg.mpg.de.
ORCID: 0000-0003-0870-0530

Andreas Trumpp (A)

Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany. a.trumpp@dkfz.de.
Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany. a.trumpp@dkfz.de.
German Cancer Consortium (DKTK), 69120, Heidelberg, Germany. a.trumpp@dkfz.de.
ORCID: 0000-0002-6212-3466

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Microvaisseaux › Artérioles › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Délétion de séquence › Délétion de gène › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance nerveuse › Nétrines › Nétrine-1 › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Niche derived netrin-1 regulates hematopoietic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Niche de cellules souches › Niche derived netrin-1 regulates hematopoietic...