Wang Lian, Jin Shengkai, Dai Peibin, Zhang Tianran, Shi Yanghua, Ai Guihai, Shao Xiaowen, Xie Yutong, Xu Jun, Chen Zhongping, Gao Zhengliang
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.
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.
Stem Cell Res. 2020 Apr;44:101759. doi: 10.1016/j.scr.2020.101759. Epub 2020 Mar 10.
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, a major CDK inhibitor, was highly expressed in quiescent and senescent hADSCs but its level quickly declined upon stem cell activation. p57 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 may be exploited for innovative strategies to amplify hADSCs of high quality for clinics.
尽管人脂肪来源干细胞（hADSCs）在再生医学领域具有巨大潜力，但其关键生物学特性仍知之甚少。特别是，由深度静止（休眠）和衰老导致的增殖缺陷是hADSC生产和临床应用中的主要障碍。我们开发了一个用于深入剖析hADSC静止和衰老机制的模型系统。p57是一种主要的CDK抑制剂，在静止和衰老的hADSCs中高表达，但其水平在干细胞激活后迅速下降。p57过表达即使在有增殖信号的情况下也会诱导静止，而其敲低即使在诱导静止的情况下也会促进细胞周期重新进入，推测这是通过调节CDK2 - CyclinE1复合物实现的。鉴于p57在静止和衰老中的关键作用，它可被用于开发创新策略，以扩增高质量的hADSCs用于临床。
