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Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging
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 in...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739444/ https://www.ncbi.nlm.nih.gov/pubmed/31303548 http://dx.doi.org/10.1016/j.stem.2019.06.007 |
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author | 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 |
author_facet | 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 |
author_sort | Ho, Ya-Hsuan |
collection | PubMed |
description | 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 β(2)-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β(3)-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β(3)-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. |
format | Online Article Text |
id | pubmed-6739444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67394442019-09-16 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 Cell Stem Cell Article 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 β(2)-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β(3)-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β(3)-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. Cell Press 2019-09-05 /pmc/articles/PMC6739444/ /pubmed/31303548 http://dx.doi.org/10.1016/j.stem.2019.06.007 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article 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 Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging |
title | Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging |
title_full | Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging |
title_fullStr | Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging |
title_full_unstemmed | Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging |
title_short | Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging |
title_sort | remodeling of bone marrow hematopoietic stem cell niches promotes myeloid cell expansion during premature or physiological aging |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739444/ https://www.ncbi.nlm.nih.gov/pubmed/31303548 http://dx.doi.org/10.1016/j.stem.2019.06.007 |
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