title: Multipotent neurogenic fate of mesenchymal stem cell is determined by Cdk4-mediated hypophosphorylation of Smad-STAT3.
abstract: Cyclin-dependent kinase (Cdk) in complex with a corresponding cyclin plays a pivotal role in neurogenic differentiation. In particular, Cdk4 activity acts as a signaling switch to direct human mesenchymal stem cells (MSCs) to neural transdifferentiation. However, the molecular evidence of how Cdk4 activity converts MSCs to neurogenic lineage remains unknown. Here, we found that Cdk4 inhibition in human MSCs enriches the populations of neural stem and progenitor pools rather than differentiated glial and neuronal cell pools. Interestingly, Cdk4 inhibition directly inactivates Smads and subsequently STAT3 signaling by hypophosphorylation, and both Cdk4 and Smads levels are linked during the processes of neural transdifferentiation and differentiation. In summary, our results provide novel molecular evidence in which Cdk4 inhibition leads to directing human MSCs to a multipotent neurogenic fate by inactivating Smads-STAT3 signaling.
authors.affiliation: a Research Core Facility, Center for Molecular Medicine, Samsung Biomedical Research Institute , Seoul , Republic of Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: b Department of Molecular Cell Biology , Sungkyunkwan University School of Medicine , Suwon, Gyeonggi , Republic of Korea.
authors.forename: Janet
authors.initials: J
authors.lastname: Lee
authors.affiliation: b Department of Molecular Cell Biology , Sungkyunkwan University School of Medicine , Suwon, Gyeonggi , Republic of Korea.
authors.forename: Dongrim
authors.initials: D
authors.lastname: Kang
authors.affiliation: b Department of Molecular Cell Biology , Sungkyunkwan University School of Medicine , Suwon, Gyeonggi , Republic of Korea.
authors.forename: Do-Hyeong
authors.initials: DH
authors.lastname: Lee
authors.affiliation: a Research Core Facility, Center for Molecular Medicine, Samsung Biomedical Research Institute , Seoul , Republic of Korea.
authors.forename: Yoon-Ja
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: c Division of Radiation Cancer Biology , Korea Institute of Radiological & Medical Sciences , Seoul , Republic of Korea.
authors.forename: Sang-Gu
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: d Department of Vascular Surgery , Sungkyunkwan University School of Medicine , Suwon, Gyeonggi , Republic of Korea.|e Samsung Seoul Hospital , Seoul , Republic of Korea.
authors.forename: Dong-Ik
authors.initials: DI
authors.lastname: Kim
authors.affiliation: a Research Core Facility, Center for Molecular Medicine, Samsung Biomedical Research Institute , Seoul , Republic of Korea.|b Department of Molecular Cell Biology , Sungkyunkwan University School of Medicine , Suwon, Gyeonggi , Republic of Korea.
authors.forename: Chang-Woo
authors.initials: CW
authors.lastname: Lee
authors.affiliation: a Research Core Facility, Center for Molecular Medicine, Samsung Biomedical Research Institute , Seoul , Republic of Korea.|f Department of Anatomy , Sungkyunkwan University School of Medicine , Suwon, Gyeonggi , Republic of Korea.
authors.forename: Kyung-Hoon
authors.initials: KH
authors.lastname: Lee
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050796:STAT3 Transcription Factor; D051785:Smad Proteins; D051358:Cyclin-Dependent Kinase 4
keywords: STAT3; Smad; cyclin-dependent kinase 4; mesenchymal stem cells; neurogenic lineage; transdifferentiation