Cyclin-dependent kinase 4 signaling acts as a molecular switch between syngenic differentiation and neural transdifferentiation in human mesenchymal stem cells
| Autor: | Hye-Young Park, Geun-Hyoung Ha, Kyo-Won Lee, Ho Park, Hyun-Chul Kim, Janet Lee, Chang Geun Lee, Dong-Yun Yang, Chang Woo Lee, Hyo Eun Moon, Jeong-Hwa Baek, Kyu-Sil Choi, Sun Ha Paek |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cell type
Cellular differentiation MAP Kinase Kinase 1 Bone Marrow Cells Cell Cycle Proteins Protein Serine-Threonine Kinases Glycogen Synthase Kinase 3 Cyclin-dependent kinase Aurora Kinases Proto-Oncogene Proteins Report CDC2 Protein Kinase Humans RNA Small Interfering Molecular Biology Cells Cultured Neurons Glycogen Synthase Kinase 3 beta biology Cyclin-dependent kinase 4 Mesenchymal stem cell Transdifferentiation Cell Cycle Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cell Differentiation Mesenchymal Stem Cells Cell Biology Cell biology Adipose Tissue Cell Transdifferentiation biology.protein Cancer research Syngenic RNA Interference Developmental Biology Signal Transduction |
| Zdroj: | Cell cycle (Georgetown, Tex.). 12(3) |
| ISSN: | 1551-4005 |
| Popis: | Multipotent mesenchymal stem/stromal cells (MSCs) are capable of differentiating into a variety of cell types from different germ layers. However, the molecular and biochemical mechanisms underlying the transdifferentiation of MSCs into specific cell types still need to be elucidated. In this study, we unexpectedly found that treatment of human adipose- and bone marrow-derived MSCs with cyclin-dependent kinase (CDK) inhibitor, in particular CDK4 inhibitor, selectively led to transdifferentiation into neural cells with a high frequency. Specifically, targeted inhibition of CDK4 expression using recombinant adenovial shRNA induced the neural transdifferentiation of human MSCs. However, the inhibition of CDK4 activity attenuated the syngenic differentiation of human adipose-derived MSCs. Importantly, the forced regulation of CDK4 activity showed reciprocal reversibility between neural differentiation and dedifferentiation of human MSCs. Together, these results provide novel molecular evidence underlying the neural transdifferentiation of human MSCs; in addition, CDK4 signaling appears to act as a molecular switch from syngenic differentiation to neural transdifferentiation of human MSCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|