%0 Journal Article
%A Ho, Ya-Hsuan
%A Del Toro, Raquel
%A Rivera-Torres, José
%A Rak, Justyna
%A Korn, Claudia
%A García-García, Andrés
%A Macías, David
%A González-Gómez, Cristina
%A Del Monte, Alberto
%A Wittner, Monika
%A Waller, Amie K
%A Foster, Holly R
%A López-Otín, Carlos
%A Johnson, Randall S
%A Nerlov, Claus
%A Ghevaert, Cedric
%A Vainchenker, William
%A Louache, Fawzia
%A Andrés, Vicente
%A Méndez-Ferrer, Simón
%T Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging.
%D 2019
%U https://hdl.handle.net/10668/27543
%X 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 β2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced β3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with β3-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.
%K Hutchinson-Gilford progeria
%K aging
%K hematopoietic stem cell
%K lymphoid
%K microenvironment
%K myeloid
%K niche
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