Oct4 and Nanog Directly Regulate Dnmt1 to Maintain Self-Renewal and Undifferentiated State in Mesenchymal Stem Cells
Copyright policy )Oct4 and Nanog Directly Regulate Dnmt1 to Maintain Self-Renewal and Undifferentiated State in Mesenchymal Stem Cells
The roles of Oct4 and Nanog in maintaining self-renewal and undifferentiated status of adult stem cells are unclear. Here, increase in Oct4 and Nanog expression along with increased proliferation and differentiation potential but decreased spontaneous differentiation were observed in early-passage (E), hypoxic culture (H), and p21 knockdown (p21KD) mesenchymal stem cells (MSCs) compared to late-passage (L), normoxic culture (N), and scrambled shRNA-overexpressed (Scr) MSCs. Knockdown of Oct4 and Nanog in E, H, and p21KD MSCs decreased proliferation and differentiation potential and enhanced spontaneous differentiation, whereas overexpression of Oct4 and Nanog in L, N, and Scr MSCs increased proliferation and differentiation potential and suppressed spontaneous differentiation. Oct4 and Nanog upregulate Dnmt1 through direct binding to its promoter, thereby leading to the repressed expression of p16 and p21 and genes associated with development and lineage differentiation. These data demonstrate the important roles of Oct4 and Nanog in maintaining MSC properties.
- National Yang Ming University Taiwan
- Taipei Veterans General Hospital Taiwan
- National Chiao Tung University Taiwan
Cyclin-Dependent Kinase Inhibitor p21, DNA (Cytosine-5-)-Methyltransferase 1, Cell Differentiation, Mesenchymal Stem Cells, Cell Biology, Models, Biological, Mice, Gene Expression Regulation, Animals, Humans, Cell Lineage, DNA (Cytosine-5-)-Methyltransferases, Hypoxia, Molecular Biology, Octamer Transcription Factor-3, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21, DNA (Cytosine-5-)-Methyltransferase 1, Cell Differentiation, Mesenchymal Stem Cells, Cell Biology, Models, Biological, Mice, Gene Expression Regulation, Animals, Humans, Cell Lineage, DNA (Cytosine-5-)-Methyltransferases, Hypoxia, Molecular Biology, Octamer Transcription Factor-3, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation
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