title: Cyclin-dependent kinase 4 signaling acts as a molecular switch between syngenic differentiation and neural transdifferentiation in human mesenchymal stem cells.
abstract: 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.
authors: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi, Korea.
authors: Janet
authors: J
authors: Lee
authors: Jeong-Hwa
authors: JH
authors: Baek
authors: Kyu-Sil
authors: KS
authors: Choi
authors: Hyun-Soo
authors: HS
authors: Kim
authors: Hye-Young
authors: HY
authors: Park
authors: Geun-Hyoung
authors: GH
authors: Ha
authors: Ho
authors: H
authors: Park
authors: Kyo-Won
authors: KW
authors: Lee
authors: Chang Geun
authors: CG
authors: Lee
authors: Dong-Yun
authors: DY
authors: Yang
authors: Hyo Eun
authors: HE
authors: Moon
authors: Sun Ha
authors: SH
authors: Paek
authors: Chang-Woo
authors: CW
authors: Lee
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D064127:Aurora Kinases; D001854:Bone Marrow Cells / Q000166:cytology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D000097869:Polo-Like Kinase 1
chemical_list: D064127:Aurora Kinases; D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D048369:MAP Kinase Kinase 1; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C495894:CDK2 protein, human; C495900:CDK4 protein, human; C482125:MAP2K1 protein, human
keywords: cell cycle arrest; cyclin-dependent kinase 4; glial cells; mesenchymal stem/stromal cells; neural cells; neurodegenerative disease; transdifferentiation