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miR-34a inhibits differentiation of human adipose tissue-derived stem cells by regulating cell cycle and senescence induction.
Differentiation, Issue: 4-5, Volume: 90, Pages: 91-100. | 2015-01-11
0 Patent citations    14 Scholarly citations     Reference Count: 37
Ho Park;Hyeon Jin Park;Ha-Jin Pak;Dong-Yun Yang;Yun-Hong Kim;Won-Jun Choi;Se-Jin Park;Jung-Ah Cho;Kyo-Won Lee

摘要

MicroRNAs (miRNAs) are critical in the maintenance, differentiation, and lineage commitment of stem cells. Stem cells have the unique property to differentiate into tissue-specific cell types (lineage commitment) during cell division (self-renewal). In this study, we investigated whether miR-34a, a cell cycle-regulating microRNA, could control the stem cell properties of adipose tissue-derived stem cells (ADSCs). First, we found that the expression level of miR-34a was increased as the cell passage number was increased. This finding, however, was inversely correlated with our finding that the overexpression of miR-34a induced the decrease of cell proliferation. In addition, miR-34a overexpression decreased the expression of various cell cycle regulators such as CDKs (−2, −4, −6) and cyclins (–E, –D), but not p21 and p53. The cell cycle analysis showed accumulation of dividing cells at S phase by miR-34a, which was reversible by co-treatment with anti-miR-34a. The potential of adipogenesis and osteogenesis of ADSCs was also decreased by miR-34a overexpression, which was recovered by co-treatment with anti-miR-34a. The surface expression of stem cell markers including CD44 was also down-regulated by miR-34a overexpression as similar to that elicited by cell cycle inhibitors. miR-34a also caused a significant decrease in mRNA expression of stem cell transcription factors as well as STAT-3 expression and phosphorylation. Cytokine profiling revealed that miR-34a significantly modulated IL-6 and -8 production, which was strongly related to cellular senescence. These data suggest the importance of miR-34a for the fate of ADSCs toward senescence rather than differentiation.


机构

Sungkyunkwan University;Wide River Institute of Immunology, Seoul National University College of Medicine,103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.Seoul National University;Medical Research Institute & Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyung-Dong, Jongro-Gu, Seoul, Republic of Korea; Department of Clinical Laboratory Science, Wonkwang Health Science University, 514 Iksandaero, Iksan, Jeonbuk, Republic of Korea.Sungkyunkwan University;Medical Research Institute & Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyung-Dong, Jongro-Gu, Seoul, Republic of Korea.Nslim clinic, Seoul, Republic of Korea.Sungkyunkwan University;Department of Anesthesiology and Pain Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Sungkyunkwan University;Department of Anesthesiology and Pain Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Sungkyunkwan University;Department of Orthopedic Surgery Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.Seoul National University;Wide River Institute of Immunology, Seoul National University College of Medicine,103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea; BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea.Sungkyunkwan University;Medical Research Institute & Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 108 Pyung-Dong, Jongro-Gu, Seoul, Republic of Korea.


文献类型:

journal article;research support, non-u.s. gov't;

出版商:

Elsevier BV

发表时间:

2015-01-11

基金信息

Samsung Biomedical Research Institute()