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

doi:10.1016/j.scr.2020.101759

p57^Kip2 is a master regulator of human adipose derived stem cell quiescence and senescence

Stem Cell Res. 2020 Apr:44:101759. doi: 10.1016/j.scr.2020.101759. Epub 2020 Mar 10.

Authors

Lian Wang¹, Shengkai Jin², Peibin Dai², Tianran Zhang², Yanghua Shi², Guihai Ai³, Xiaowen Shao¹, Yutong Xie⁴, Jun Xu⁵, Zhongping Chen⁶, Zhengliang Gao⁷

Affiliations

¹ 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.
² 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.
³ 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.
⁴ Tongji University Cancer Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
⁵ East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: Xunymc2000@yahoo.com.
⁶ 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. Electronic address: mdchen18@tongji.edu.cn.
⁷ 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. Electronic address: zhengliang_gao@tongji.edu.cn.

PMID: 32224418
DOI: 10.1016/j.scr.2020.101759

Abstract

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. p57^Kip2, a major CDK inhibitor, was highly expressed in quiescent and senescent hADSCs but its level quickly declined upon stem cell activation. p57^Kip2 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, p57^Kip2 may be exploited for innovative strategies to amplify hADSCs of high quality for clinics.

Keywords: Human adipose derived stem cells; Quiescence; Senescence; p57(Kip2).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle
Cell Cycle Checkpoints
Cell Division
Cyclin-Dependent Kinase Inhibitor p57* / genetics
Humans
Stem Cells*

Substances

Cyclin-Dependent Kinase Inhibitor p57