RT Journal Article
T1 Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging.
A1 Ho, Ya-Hsuan
A1 Del Toro, Raquel
A1 Rivera-Torres, José
A1 Rak, Justyna
A1 Korn, Claudia
A1 García-García, Andrés
A1 Macías, David
A1 González-Gómez, Cristina
A1 Del Monte, Alberto
A1 Wittner, Monika
A1 Waller, Amie K
A1 Foster, Holly R
A1 López-Otín, Carlos
A1 Johnson, Randall S
A1 Nerlov, Claus
A1 Ghevaert, Cedric
A1 Vainchenker, William
A1 Louache, Fawzia
A1 Andrés, Vicente
A1 Méndez-Ferrer, Simón
K1 Hutchinson-Gilford progeria
K1 aging
K1 hematopoietic stem cell
K1 lymphoid
K1 microenvironment
K1 myeloid
K1 niche
AB 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.
YR 2019
FD 2019-07-11
LK https://hdl.handle.net/10668/27543
UL https://hdl.handle.net/10668/27543
LA en
DS RISalud
RD Apr 15, 2025