Very low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations that differ by their cell cycling, differentiation and p27(KIP1) expression

Oxygen (O-2) concentrations in bone marrow vary from 4% in capillaries to <0.1% in subendosteum, in which hematopoietic stem cells reside in specific niches. Culture at low O-2 concentrations (3, 1 and 0.1%) influences hematopoietic stem and progenitor cells survival, proliferation and differentiation, depending on their level of differentiation. Culture of human CD34(+) cells at low O-2 concentrations (O-2 <= 3%) maintains stem cell engraftment potential better than at 20% O-2 (NOD/Scid xenograft model). In contrast, progenitors disappear from cultures at/or <1% O-2 concentrations. A very low O-2 concentration (0.1%) induces CD34(+) quiescence in G(0). The exploration of molecules and mechanisms involved in hematopoietic stem and progenitor cells' quiescence and differentiation related to low O-2 concentrations is unfeasible with primary CD34(+) cells. Therefore, we performed it using murine hematopoietic nonleukemic factor-dependent cell Paterson (FDCP)-Mix progenitor cell line. The culture of the FDCP-Mix line at 0.1% O-2 induced in parallel G(0) quiescence and granulo-monocytic differentiation of most cells, whereas a minority of undifferentiated self-renewing cells remained in active cell cycle. Hypoxia also induced hypophosphorylation of pRb and increased the expression of p27(KIP1), the two proteins that have a major role in the control of G(0) and G(1) to S-phase transition. Cell Death and Differentiation (2011) 18, 174-182; doi: 10.1038/cdd.2010.85; published online 30 July 2010