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衰老过程中BM细胞的扩增机制获揭示
作者:小柯机器人 发布时间:2019/9/6 15:10:25

英国剑桥大学Simón Méndez-Ferrer团队发现了骨髓造血干细胞(HSC)生态位的重塑,在早衰或者生理衰老过程中促进骨髓(BM)细胞的扩增机制。该研究于2019年9月发表在《细胞—干细胞》上。

研究发现BM微环境促进过早衰或者生理衰老人群的骨髓细胞生成。在生理衰老期间,支持造血干细胞(HSC)的壁龛在骨附近减少但从远处扩增。增加的BM中去神经支配的去甲肾上腺素促进β2-肾上腺素能受体(AR)-白细胞介素-6依赖的巨核细胞生成。β3-AR-Nos1活性降低与骨内膜细胞减少,和巨核细胞与窦状隙的附着有关。然而,用β3-AR激动剂长期治疗早衰小鼠可减少早期骨髓和HSC扩增,并恢复HSC与巨核细胞的近端关联。因此,BM龛的正常衰老或者早衰促进骨髓扩增,并且可以通过靶向微环境来改善。

研究人员表示,存在于BM中的HSC虽然在衰老期间累积但在功能上是受损的。然而,HSC-内在和外在衰老机制仍然存在争议。巨核细胞促进邻近HSC的静止。尽管如此,在病理或者自然衰老过程中,巨核细胞与HSC是否发生相互作用变化尚不清楚。 Hutchinson-Gilford早衰综合征可以概括出生理性衰老的特征,但这些特征是否由干细胞或生态位细胞改变引起,尚不清楚。

附:英文原文

Title: Remodeling of Bone Marrow Hematopoietic Stem Cell Niches Promotes Myeloid Cell Expansion during Premature or Physiological Aging

Author: Ya-Hsuan Ho, Raquel del Toro, José Rivera-Torres, Justyna Rak, Claudia Korn, Andrés García-García, David Macías, Cristina González-Gómez, Alberto del Monte, Monika Wittner, Amie K. Waller, Holly R. Foster, Carlos López-Otín, Randall S. Johnson, Claus Nerlov, Cedric Ghevaert, William Vainchenker, Fawzia Louache, Vicente Andrés, Simón Méndez-Ferrer

Issue&Volume:Volume 25 Issue 3

Abstract: 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.

DOI: 10.1016/j.stem.2019.06.007

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30271-1

期刊信息

Cell Stem Cell:《细胞—干细胞》,创刊于2007年。隶属于细胞出版社,最新IF:21.464
官方网址:https://www.cell.com/cell-stem-cell/home
投稿链接:https://www.editorialmanager.com/cell-stem-cell/default.aspx