Hypoxia Upregulates Mitotic Cyclins Which Contribute to the Multipotency of Human Mesenchymal Stem Cells by Expanding Proliferation Lifespan
Janet Lee1,2, Hyun-Soo Kim1, Su-Min Kim1, Dong-Ik Kim3,*, and Chang-Woo Lee1,4,*
1Department of Molecular Cell Biology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Suwon 16419, Korea, 2Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea, 3Department of Vascular Surgery, Samsung Seoul Hospital, Sungkyunkwan University School of Medicine, Seoul 06351, Korea, 4Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon 16419, Korea
*Correspondence: cwlee1234@skku.edu (CWL); dikim@skku.edu (DIK)
Received September 22, 2017; Revised December 20, 2017; Accepted December 26, 2017.; Published online February 21, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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Hypoxic culture is widely recognized as a method to efficiently expand human mesenchymal stem cells (MSCs) without loss of stem cell properties. However, the molecular basis of how hypoxia priming benefits MSC expansion remains unclear. In this report, our systemic quantitative proteomic and RT-PCR analyses revealed the involvement of hypoxic conditioning activated genes in the signaling process of the mitotic cell cycle. Introduction of screened two mitotic cyclins, CCNA2 and CCNB1, significantly extended the proliferation lifespan of MSCs in normoxic condition. Our results provide important molecular evidence that multipotency of human MSCs by hypoxic conditioning is determined by the mitotic cell cycle duration. Thus, the activation of mitotic cyclins could be a potential strategy to the application of stem cell therapy.
Keywords: cell proliferation lifespan, cyclin, multipotency, mitosis, human mesenchymal stem cell, hypoxia

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28 February 2018 Volume 41,
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