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Niche derived netrin-1 regulates hematopoietic stem cell dormancy via its receptor neogenin-1.
Renders, Simon; Svendsen, Arthur Flohr; Panten, Jasper; Rama, Nicolas; Maryanovich, Maria; Sommerkamp, Pia; Ladel, Luisa; Redavid, Anna Rita; Gibert, Benjamin; Lazare, Seka; Ducarouge, Benjamin; Schönberger, Katharina; Narr, Andreas; Tourbez, Manon; Dethmers-Ausema, Bertien; Zwart, Erik; Hotz-Wagenblatt, Agnes; Zhang, Dachuan; Korn, Claudia; Zeisberger, Petra; Przybylla, Adriana; Sohn, Markus; Mendez-Ferrer, Simon; Heikenwälder, Mathias; Brune, Maik; Klimmeck, Daniel; Bystrykh, Leonid; Frenette, Paul S; Mehlen, Patrick; de Haan, Gerald; Cabezas-Wallscheid, Nina; Trumpp, Andreas.
Afiliación
  • Renders S; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
  • Svendsen AF; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
  • Panten J; Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany.
  • Rama N; 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.
  • Maryanovich M; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
  • Sommerkamp P; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
  • Ladel L; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
  • 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.
  • Gibert B; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Lazare S; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Ducarouge B; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Schönberger K; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
  • Narr A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
  • Tourbez M; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
  • Dethmers-Ausema B; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
  • Zwart E; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
  • Hotz-Wagenblatt A; 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.
  • Zhang D; 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.
  • Korn C; 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.
  • Zeisberger 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.
  • Przybylla A; Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg, Germany.
  • Sohn M; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, 69120, Heidelberg, Germany.
  • Mendez-Ferrer S; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), 69120, Heidelberg, Germany.
  • Heikenwälder M; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
  • Brune 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.
  • Klimmeck D; 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.
  • 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.
  • Frenette PS; Core Facility Omics IT and Data Management, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Mehlen P; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY, USA.
  • de Haan G; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Cabezas-Wallscheid N; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Trumpp A; Wellcome Trust/MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AH, UK.
Nat Commun ; 12(1): 608, 2021 01 27.
Article en En | MEDLINE | ID: mdl-33504783
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Nicho de Células Madre / Netrina-1 / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Nicho de Células Madre / Netrina-1 / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido