Very low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations that differ by their cell cycling, differentiation and p27KIP1 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.
Guitart
A V
AV
Université de Bordeaux, Bordeaux, France.
Debeissat
C
C
Hermitte
F
F
Villacreces
A
A
Ivanovic
Z
Z
Boeuf
H
H
Praloran
V
V
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D015687:Cell Hypoxia; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D016193:G1 Phase; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D019707:Receptors, Chemokine / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D018952:Antigens, CD34; C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine; D016160:Retinoblastoma Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010100:Oxygen