title: Cell cycle regulators are critical for maintaining the differentiation potential and immaturity in adipogenesis of adipose-derived stem cells.
abstract: A single cell division is governed by the catalytic reactions of cyclins and cyclin-dependent kinases (CDKs). Stem cells are unique in that they can differentiate into tissue-specific cell types (lineage commitment) during cell division (self-renewal). In this study, we analyzed changes in the differentiation potency of adipose tissue-derived stem cells (ADSCs) according to the number of spontaneous cell divisions. We used low passage number (p3) to late passage number (p60) adipose-derived stem cells (ADSCs) as our model system. A preliminary investigation of the typical stem cell phenotypes revealed that CD44 expression decreased remarkably as the passage number of the ADSCs increased. Further examinations revealed that the higher the cell passage number, the lower the cell proliferation capability, differentiation potency, and expression of stem cell transcriptional factors and cell cycle regulators such as cyclins E, A, B, CDK2, and CDK1/CDC2. To verify if the observed changes in differentiation potency according to the number of cell divisions were related to cell cycle regulators, p3 ADSCs were treated with the selective CDK2 and CDK1/CDC2 inhibitor Purvalanol A. Inhibitor treatment of p3 ADSCs induced changes in the morphology, differentiation potency, and pattern of stem cell transcriptional factor expression so that these low passage ADSCs more closely resembled high-passage ADSCs. Collectively, our results indicate that cell cycle regulators control the differentiation potency of ADSCs, and provide insights into the cell biology and differentiation potency of ADSCs according to the number of cell divisions.
authors.affiliation: Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Park
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Cho
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Lim
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Lee
authors.forename: Sang
authors.initials: S
authors.lastname: Won Seo
authors.forename: Dong Yun
authors.initials: DY
authors.lastname: Yang
authors.forename: Kyo Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D002452:Cell Count; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016213:Cyclins; D014157:Transcription Factors; D018844:Cyclin-Dependent Kinases