Foxo3a is essential for maintenance of the hematopoietic stem cell pool

Hematopoietic stem cells (HSCs) are maintained in an undifferentiated quiescent state within a bone marrow niche. Here we show that Foxo3a, a forkhead transcription factor that acts downstream of the PTEN/PI3K/Akt pathway, is critical for HSC self-renewal. We generated gene-targeted Foxo3a−/− mice and showed that, although the proliferation and differentiation of Foxo3a−/− hematopoietic progenitors were normal, the number of colony-forming cells present in long-term cocultures of Foxo3a−/− bone marrow cells and stromal cells was reduced. The ability of Foxo3a−/− HSCs to support long-term reconstitution of hematopoiesis in a competitive transplantation assay was also impaired. Foxo3a−/− HSCs also showed…

• MO
  Ministry of Education, Culture, Sports, Science and Technology
• MO
  Ministry of Health, Labour and Welfare
• NI
  National Institutes of Health