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Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging.
Ho, Ya-Hsuan; Del Toro, Raquel; Rivera-Torres, José; Rak, Justyna; Korn, Claudia; García-García, Andrés; Macías, David; González-Gómez, Cristina; Del Monte, Alberto; Wittner, Monika; Waller, Amie K; Foster, Holly R; López-Otín, Carlos; Johnson, Randall S; Nerlov, Claus; Ghevaert, Cedric; Vainchenker, William; Louache, Fawzia; Andrés, Vicente; Méndez-Ferrer, Simón.
Afiliación
  • Ho YH; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Del Toro R; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBER-CV), Spain.
  • Rivera-Torres J; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBER-CV), Spain.
  • Rak J; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Korn C; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • García-García A; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK; Centro Nacional de Investigaciones Cardiovasculares (
  • Macías D; Physiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
  • González-Gómez C; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBER-CV), Spain.
  • Del Monte A; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBER-CV), Spain.
  • Wittner M; INSERM (Institut National de la Santé et de la Recherche Médicale), Université Paris-Saclay, UMR1170, Gustave Roussy, 94805 Villejuif, France; Université Paris-Saclay and CNRS GDR 3697 MicroNiT, Villejuif, France.
  • Waller AK; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Foster HR; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • López-Otín C; Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain; Centro de Investigación Biomédica en Red de Cáncer, CIBERONC, Madrid, Spain.
  • Johnson RS; Physiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
  • Nerlov C; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
  • Ghevaert C; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK.
  • Vainchenker W; INSERM (Institut National de la Santé et de la Recherche Médicale), Université Paris-Saclay, UMR1170, Gustave Roussy, 94805 Villejuif, France.
  • Louache F; INSERM (Institut National de la Santé et de la Recherche Médicale), Université Paris-Saclay, UMR1170, Gustave Roussy, 94805 Villejuif, France; Université Paris-Saclay and CNRS GDR 3697 MicroNiT, Villejuif, France.
  • Andrés V; Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; CIBER de Enfermedades Cardiovasculares (CIBER-CV), Spain.
  • Méndez-Ferrer S; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Cambridge CB2 0PT, UK; Centro Nacional de Investigaciones Cardiovasculares (
Cell Stem Cell ; 25(3): 407-418.e6, 2019 09 05.
Article en En | MEDLINE | ID: mdl-31303548
ABSTRACT
Hematopoietic stem cells (HSCs) residing in the bone marrow (BM) accumulate during aging but are functionally impaired. However, the role of HSC-intrinsic and -extrinsic aging mechanisms remains debated. Megakaryocytes promote quiescence of neighboring HSCs. Nonetheless, whether megakaryocyte-HSC interactions change during pathological/natural aging is unclear. Premature aging in Hutchinson-Gilford progeria syndrome recapitulates physiological aging features, but whether these arise from altered stem or niche cells is unknown. Here, we show that the BM microenvironment promotes myelopoiesis in premature/physiological aging. During physiological aging, HSC-supporting niches decrease near bone but expand further from bone. Increased BM noradrenergic innervation promotes ß2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced ß3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with ß3-AR agonist decreases premature myeloid and HSC expansion and restores the proximal association of HSCs to megakaryocytes. Therefore, normal/premature aging of BM niches promotes myeloid expansion and can be improved by targeting the microenvironment.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Progeria / Médula Ósea / Envejecimiento / Células Madre Hematopoyéticas / Megacariocitos / Envejecimiento Prematuro / Células Mieloides Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Progeria / Médula Ósea / Envejecimiento / Células Madre Hematopoyéticas / Megacariocitos / Envejecimiento Prematuro / Células Mieloides Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido