FoxO3a regulates hematopoietic homeostasis through a negative feedback pathway in conditions of stress or aging

Kana Miyamoto, Takeshi Miyamoto, Reiko Kato, Akihiko Yoshimura, Noboru Motoyama, Toshio Suda

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Stress or aging of tissue-specific stem cells is considered central to the decline of tissue homeostasis in the elderly, although little is known of molecular mechanisms underlying hematopoietic stem cell (HSC) aging and stress resistance. Here, we report that mice lacking the transcription factor forkhead box O3a (FoxO3a) develop neutrophilia associated with inhibition of the up-regulation of negative regulator of cell proliferation, Sprouty-related Ena/VASP homology 1 domain-containing proteins 2 (Spred2) and AKT and ERK activation, in HSCs during hema-topoietic recovery following myelosup-pressive stress conditions. Compared with aged wild-type mice, more severe neutrophilia was also observed in aged Foxo3a-deficient mice. AKT and ERK activation and inhibition of Spred2 were detected in HSCs from aged FoxO3a-deficient mice. Spred2-deficient mice also developed neutrophilia during hematopoietic recovery following myelosuppressive stress, indicating that FoxO3a plays a pivotal role in maintenance, integrity, and stress resistance of HSCs through negative feedback pathways for proliferation. This will provide new insight into the hematopoietic homeostasis in conditions of aging and stress.

Original languageEnglish
Pages (from-to)4485-4493
Number of pages9
JournalBlood
Volume112
Issue number12
DOIs
Publication statusPublished - 2008 Dec 1

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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