p38α plays differential roles in hematopoietic stem cell activity dependent on aging contexts

Yuriko Sorimachi, Daiki Karigane, Yukako Ootomo, Hiroshi Kobayashi, Takayuki Morikawa, Kinya Otsu, Yoshiaki Kubota, Shinichiro Okamoto, Nobuhito Goda, Keiyo Takubo

研究成果: Article査読

抄録

Hematopoietic stem cells (HSCs) and their progeny sustain lifetime hematopoiesis. Aging alters HSC function, number, and composition and increases risk of hematological malignancies, but how these changes occur in HSCs remains unclear. Signaling via p38 mitogen-activated kinase (p38MAPK) has been proposed as a candidate mechanism underlying induction of HSC aging. Here, using genetic models of both chronological and premature aging, we describe a multimodal role for p38α, the major p38MAPK isozyme in hematopoiesis, in HSC aging. We report that p38α regulates differentiation bias and sustains transplantation capacity of HSCs in the early phase of chronological aging. However, p38α decreased HSC transplantation capacity in the late progression phase of chronological aging. Furthermore, codeletion of p38α in mice deficient in ataxia-telangiectasia mutated, a model of premature aging, exacerbated aging-related HSC phenotypes seen in ataxia- telangiectasia mutated single-mutant mice. Overall, these studies provide new insight into multiple functions of p38MAPK, which both promotes and suppresses HSC aging context dependently.

本文言語English
論文番号100563
ジャーナルJournal of Biological Chemistry
296
DOI
出版ステータスPublished - 2021 1 1
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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