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

TitleVery low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations that differ by their cell cycling, differentiation and p27KIP1 expression.
Publication TypeJournal Article
Year of Publication2011
AuthorsGuitart A, Debeissat C, Hermitte F, Villacreces A, Ivanovic Z, Boeuf H, Praloran V
JournalCell Death Differ
Volume18
Issue1
Pagination174-82
Date Published2011 Jan
ISSN1476-5403
KeywordsAnimals, Antigens, CD34, Cell Differentiation, Cell Hypoxia, Cyclin-Dependent Kinase Inhibitor p27, G0 Phase, G1 Phase, Hematopoietic Stem Cells, Humans, Mice, Oxygen, Phosphorylation, Receptors, Chemokine, Retinoblastoma Protein, S Phase, Stem Cells
Abstract

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.

DOI10.1038/cdd.2010.85
Alternate JournalCell Death Differ.
PubMed ID20671746
PubMed Central IDPMC3131863
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