2026-06-14T10:37:40Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83312024-09-27T09:16:25Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Ho, Ya-Hsuan author Del Toro, Raquel author Rivera-Torres, Jose author Rak, Justyna author Korn, Claudia author Garcia-Garcia, Andres author Macías, David author Gonzalez-Gomez, Cristina author del Monte, Alberto author Wittner, Monika author Waller, Amie K author Foster, Holly R author López-Otín, Carlos author Johnson, Randall S author Nerlov, Claus author Ghevaert, Cedric author Vainchenker, William author Louache, Fawzia author Andres, Vicente author Mendez-Ferrer, Simon author 2019-09-05 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. Cell Stem Cell. 2019; 25(3):407-18 10.1016/j.stem.2019.06.007 1875-9777 19345909 Cell stem cell 31303548 http://hdl.handle.net/20.500.12105/8331 Hutchinson-Gilford progeria Aging Hematopoietic stem cell Lymphoid Microenvironment Myeloid Niche Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging