Very low oxygen concentration (0.1%) reveals two FDCP-Mix cells subpopulations that differ by their cell cycling, differentiation and p27KIP1 expression

Vincent Praloran (1) , Amélie Guitart (1) , Christelle Debeissat (1) , Francis Hermitte (1) , Arnaud Villacreces (1) , Zoran Ivanovic (1) , Helene Boeuf (1)

1 CIRID - Composantes innées de la réponse immunitaire et différenciation

Oxygen concentrations in bone marrow vary from 4% in capillaries to less than 0.1% in subendosteum where hematopoietic stem cells reside in specific niches. Culture at low O2 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 O2 concentrations (O2 ≤ 3%) maintains stem cell engraftment potential better than at 20% O2 (NOD/Scid xenograft model). In contrast, progenitors disappear from cultures at/or below 1% O2 concentrations. A very low O2 concentration (0.1%) induces CD34+ quiescence in G0. The exploration of molecules and mechanisms involved in hematopoietic stem and progenitor cells' quiescence and differentiation related to low O2 concentrations is unfeasible with primary CD34+ cells. Therefore, we performed it using murine hematopoietic non leukemic FDCP-Mix progenitor cell line. The culture of the FDCP-Mix line at 0.1% O2 induced in parallel G0 quiescence and granulo-monocytic differentiation of most cells, while a minority of undifferentiated self-renewing cells remains in active cell cycle. Hypoxia also induced hypophosphorylation of pRb and increased the expression of p27KIP1, two proteins that play a major role in the control of G0 and G1 to S phase transition.

Mots clés: hematopoiesis; hypoxia; cell cycle; quiescence; differentiation

Vincent Praloran, Amélie Guitart, Christelle Debeissat, Francis Hermitte, Arnaud Villacreces, et al.. Very low oxygen concentration (0.1%) reveals two FDCP-Mix cells subpopulations that differ by their cell cycling, differentiation and p27KIP1 expression. Cell Death and Differentiation, 2010, ⟨10.1038/cdd.2010.85⟩. ⟨hal-00560771⟩