p57Kip2 is a master regulator of human adipose derived stem cell quiescence and senescence

Lian Wang; Shengkai Jin; Peibin Dai; Tianran Zhang; Yanghua Shi; Guihai Ai; Xiaowen Shao; Yutong Xie; Jun Xu; Zhongping Chen; Zhengliang Gao

Stem Cell Research (Apr 2020)

p57Kip2 is a master regulator of human adipose derived stem cell quiescence and senescence

Lian Wang,
Shengkai Jin,
Peibin Dai,
Tianran Zhang,
Yanghua Shi,
Guihai Ai,
Xiaowen Shao,
Yutong Xie,
Jun Xu,
Zhongping Chen,
Zhengliang Gao

Affiliations

Lian Wang: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China
Shengkai Jin: Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China; Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai 200092 China
Peibin Dai: Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China; Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai 200092 China
Tianran Zhang: Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China; Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai 200092 China
Yanghua Shi: Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China; Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai 200092 China
Guihai Ai: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Xiaowen Shao: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China
Yutong Xie: Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
Jun Xu: East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Corresponding author.
Zhongping Chen: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding authors at: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Zhengliang Gao: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Gynecologic Minimally Invasive Surgery Research Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; The Lifeng institute of Regenerative Medicine, Tongji University, Shanghai 200092, China; Advanced Institute of Translational Medicine, Tongji University School of Medicine, Shanghai 200092 China; Corresponding authors at: Department of Gynecology and Obstetrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Journal volume & issue: Vol. 44

Abstract

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Although human adipose derived stem cells (hADSCs) hold great promises for regenerative medicine, their key biological properties remain poorly understood. In particular, proliferation defects resulted from deep quiescence (dormancy) and senescence represent a major hurdle in hADSC production and clinical application. We have developed a model system for mechanistic dissection of hADSC quiescence and senescence. p57Kip2, a major CDK inhibitor, was highly expressed in quiescent and senescent hADSCs but its level quickly declined upon stem cell activation. p57Kip2 overexpression induced quiescence in spite of proliferative signals and its knockdown promoted cell cycle reentry even with induction of quiescence presumably through modulating the CDK2–CyclinE1 complex. Given its key role in quiescence and senescence, p57Kip2 may be exploited for innovative strategies to amplify hADSCs of high quality for clinics. Keywords: Human adipose derived stem cells, p57Kip2, Quiescence, Senescence

Published in Stem Cell Research

ISSN: 1873-5061 (Print); 1876-7753 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: https://www.journals.elsevier.com/stem-cell-research

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