| First Author | Ho YH | Year | 2019 |
| Journal | Cell Stem Cell | Volume | 25 |
| Issue | 3 | Pages | 407-418.e6 |
| PubMed ID | 31303548 | Mgi Jnum | J:287249 |
| Mgi Id | MGI:6390745 | Doi | 10.1016/j.stem.2019.06.007 |
| Citation | Ho YH, et al. (2019) Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging. Cell Stem Cell 25(3):407-418.e6 |
| abstractText | 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 beta2-adrenergic-receptor(AR)-interleukin-6-dependent megakaryopoiesis. Reduced beta3-AR-Nos1 activity correlates with decreased endosteal niches and megakaryocyte apposition to sinusoids. However, chronic treatment of progeroid mice with beta3-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. |
