المؤلفون: Fielding, Claire, García-García, Andrés, Korn, Claudia, Gadomski, Stephen, Fang, Zijian, Reguera, Juan L, Pérez-Simón, José A, Gottgens, Berthold, Méndez-Ferrer, Simón

المساهمون: National Institutes of Health (US), International Scholarship at The University of Cambridge, European Commission, European Research Council, MRC Cambridge Stem Cell Institute, National Health Institute Blood and Transplant (UK), Cancer Research UK, Wellcome Trust, García-García, Andrés [0000-0002-8797-649X], Pérez-Simón, José A [0000-0003-3616-6101], Göttgens, Berthold [0000-0001-6302-5705], Méndez-Ferrer, Simón [0000-0002-9805-9988], Apollo - University of Cambridge Repository, Universidad de Sevilla. Departamento de Medicina, Gottgens, Berthold [0000-0001-6302-5705]

المصدر: Nature Communications, Vol 13, Iss 1, Pp 1-13 (2022)
Digital.CSIC. Repositorio Institucional del CSIC
instname
Nature Communications

مصطلحات موضوعية: Glial Cell Line-Derived Neurotrophic Factor Receptors, Science, Cholinergic Agents, General Physics and Astronomy, 13/106, Haematopoietic stem, General Biochemistry, Genetics and Molecular Biology, 631/532/2139, 13/1, Mice, 13/100, Bone Marrow, Risk Factors, 631/443/63, Animals, Humans, 14/19, Bone, 49/91, 631/532/2118/1542, Multidisciplinary, Cambridge Stem Cell Institute, Haematopoietic stem cells, article, Hematopoietic Stem Cell Transplantation, Mesenchymal Stem Cells, General Chemistry, Hematopoietic Stem Cells, Chemokine CXCL12, Hematopoiesis, 13/31, Cholinergic signals, Receptors, Adrenergic, beta-3, 13/51, 14/63, 692/499, Stem-cell niche, Regenerative haematopoiesis

الوصف: The sympathetic nervous system has been evolutionary selected to respond to stress and activates haematopoietic stem cells via noradrenergic signals. However, the pathways preserving haematopoietic stem cell quiescence and maintenance under proliferative stress remain largely unknown. Here we found that cholinergic signals preserve haematopoietic stem cell quiescence in bone-associated (endosteal) bone marrow niches. Bone marrow cholinergic neural signals increase during stress haematopoiesis and are amplified through cholinergic osteoprogenitors. Lack of cholinergic innervation impairs balanced responses to chemotherapy or irradiation and reduces haematopoietic stem cell quiescence and self-renewal. Cholinergic signals activate α7 nicotinic receptor in bone marrow mesenchymal stromal cells leading to increased CXCL12 expression and haematopoietic stem cell quiescence. Consequently, nicotine exposure increases endosteal haematopoietic stem cell quiescence in vivo and impairs hematopoietic regeneration after haematopoietic stem cell transplantation in mice. In humans, smoking history is associated with delayed normalisation of platelet counts after allogeneic haematopoietic stem cell transplantation. These results suggest that cholinergic signals preserve stem cell quiescence under proliferative stress.
The sympathetic nervous system has been shown to respond to stress and activate haematopoietic stem cells. Here they show that cholinergic signals in the bone marrow preserve haematopoietic stem cell quiescence and self-renewal under proliferative stress.

وصف الملف: application/pdf; application/zip; text/xml

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::19c19135813718229894b3a5083e7954
https://doi.org/10.1038/s41467-022-28175-1

المؤلفون: Luisa Ladel, Anna Rita Redavid, Erik Zwart, Leonid Bystrykh, Patrick Mehlen, Benjamin Gibert, Jasper Panten, Maik Brune, Mathias Heikenwalder, Bertien Dethmers-Ausema, Katharina Schönberger, Dachuan Zhang, Maria Maryanovich, Pia Sommerkamp, Simon Renders, Simón Méndez-Ferrer, Andreas Narr, Markus Sohn, Manon Tourbez, Claudia Korn, Petra Zeisberger, Seka Lazare, Andreas Trumpp, Agnes Hotz-Wagenblatt, Benjamin Ducarouge, Gerald de Haan, Paul S. Frenette, Adriana Przybylla, Arthur Flohr Svendsen, Nina Cabezas-Wallscheid, Nicolas Rama, Daniel Klimmeck

المساهمون: German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg Institute for Stem Cell Technology and Experimental Medicine, Heidelberg University Hospital [Heidelberg], University of Groningen [Groningen], Heidelberg University, Développement Cancer et Thérapies Ciblées [Lyon] (LabEx DEVweCAN), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Albert Einstein College of Medicine [New York], Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, University of Cambridge [UK] (CAM), NHS Blood and Transplant [London, UK], German Cancer Consortium [Heidelberg] (DKTK), Stem Cell Aging Leukemia and Lymphoma (SALL), Rama, Nicolas [0000-0003-1614-7755], Maryanovich, Maria [0000-0002-2015-0538], Gibert, Benjamin [0000-0002-5295-3124], Zwart, Erik [0000-0002-4552-003X], Zhang, Dachuan [0000-0002-1746-275X], Mendez-Ferrer, Simon [0000-0002-9805-9988], Heikenwälder, Mathias [0000-0002-3135-2274], Bystrykh, Leonid [0000-0001-6924-5602], Frenette, Paul S [0000-0003-0862-9922], de Haan, Gerald [0000-0001-9706-0138], Cabezas-Wallscheid, Nina [0000-0003-0870-0530], Trumpp, Andreas [0000-0002-6212-3466], Apollo - University of Cambridge Repository, Frenette, Paul S. [0000-0003-0862-9922]

المصدر: Nature Communications
Nature Communications, Nature Publishing Group, 2021, 12 (1), ⟨10.1038/s41467-020-20801-0⟩
Nature Communications, 12(1):608. Nature Publishing Group
Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021)

مصطلحات موضوعية: 0301 basic medicine, Cellular differentiation, [SDV]Life Sciences [q-bio], General Physics and Astronomy, 631/532/2441, Transgenic, Mice, 0302 clinical medicine, Netrin, Hematopoietic Stem Cells/metabolism, 14/19, Stem Cell Niche, Cellular Senescence, Multidisciplinary, Haematopoietic stem cells, Arterioles/metabolism, Hematopoietic Stem Cell Transplantation, Hematopoietic stem cell, Cell Differentiation, Netrin-1, 3. Good health, Cell biology, 13/31, Mutant Strains, Haematopoiesis, Arterioles, medicine.anatomical_structure, Self-renewal, 64/60, Stem cell, Signal Transduction, Stromal cell, Science, 13/106, Mice, Transgenic, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 38/91, 631/532/2139, 03 medical and health sciences, 13/100, Downregulation and upregulation, medicine, Animals, Cell Proliferation, 631/443/7, Membrane Proteins, General Chemistry, Hematopoietic Stem Cells, 631/532/1542, Mice, Mutant Strains, Ageing, 030104 developmental biology, 13/51, Netrin-1/metabolism, Membrane Proteins/metabolism, Bone marrow, 030217 neurology & neurosurgery, Stem-cell niche, Gene Deletion

الوصف: 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.

وصف الملف: application/pdf; application/zip; text/xml

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d312e76c9a193f9fd3948cd0cb57454a
http://europepmc.org/articles/PMC7840807

المؤلفون: 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

مصطلحات موضوعية: 13/31, 631/532/2139, 13/100, 631/443/7, 13/51, article, 13/106, 64/60, 631/532/2441, 14/19, 631/532/1542, 3. Good health, 38/91

الوصف: 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
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.

URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::8702c7ae82f3d82ffb1118c5b7683e08