PMID- 16926163 OWN - NLM STAT- MEDLINE DCOM- 20061127 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 281 IP - 41 DP - 2006 Oct 13 TI - Differentiation arrest by hypoxia. PG - 30678-83 AB - The stem cell niche is a unique tissue microenvironment that regulates the self-renewal and differentiation of stem cells. Although several stromal cells and molecular pathways have been identified, the microenvironment of the stem cell niche remains largely unclear. Recent evidence suggests that stem cells are localized in areas with low oxygen. We have hypothesized that hypoxia maintains the undifferentiated phenotype of stem/precursor cells. In this report, we demonstrate that hypoxia reversibly arrests preadipocytes in an undifferentiated state. Consistent with this observation, hypoxia maintains the expression of pref-1, a key stem/precursor cell gene that negatively regulates adipogenic differentiation. We further demonstrate that the hypoxia-inducible factor-1 (HIF-1) constitutes an important mechanism for the inhibition of adipogenic differentiation by hypoxia. Our findings suggest that hypoxia in the stem cell niche is critical for the maintenance of the undifferentiated stem or precursor cell phenotype. FAU - Lin, Qun AU - Lin Q AD - Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. FAU - Lee, Yi-Jang AU - Lee YJ FAU - Yun, Zhong AU - Yun Z LA - eng PT - Journal Article DEP - 20060822 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Hif1a protein, mouse) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - S88TT14065 (Oxygen) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/metabolism MH - Adipose Tissue/cytology/metabolism MH - Animals MH - Cell Differentiation MH - *Hypoxia MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Oxygen/metabolism MH - Phenotype MH - Stem Cells/cytology EDAT- 2006/08/24 09:00 MHDA- 2006/12/09 09:00 CRDT- 2006/08/24 09:00 PHST- 2006/08/24 09:00 [pubmed] PHST- 2006/12/09 09:00 [medline] PHST- 2006/08/24 09:00 [entrez] AID - S0021-9258(19)89282-7 [pii] AID - 10.1074/jbc.C600120200 [doi] PST - ppublish SO - J Biol Chem. 2006 Oct 13;281(41):30678-83. doi: 10.1074/jbc.C600120200. Epub 2006 Aug 22.