Wang Yuan, Sui Yutong, Lian Aobo, Han Xing, Liu Feilin, Zuo Kuiyang, Liu Mingsheng, Sun Wei, Wang Ziyu, Liu Zinan, Zou Fei, Lu Rifeng, Jin Minghua, Du Haiying, Xu Kan, Liu Xiaomei, Liu Jinyu
Department of Toxicology, School of Public Health, Jilin University, Changchun, China.
Eye Center, The Second Hospital of Jilin University, Changchun, China.
Front Cell Dev Biol. 2021 Nov 15;9:739868. doi: 10.3389/fcell.2021.739868. eCollection 2021.
Tissues and organs undergo structural deterioration and functional decline during aging. DNA damage is considered a major cause of stem cell senescence. Although stem cells develop sophisticated DNA repair systems, when the intrinsic and extrinsic insults exceed the DNA repair capacity, cellular senescence, and age-related diseases inevitably occur. Therefore, the prevention and alleviation of DNA damage is an alternative to DNA repair in attenuating stem cell senescence and preventing age-related diseases. Pre-B-cell leukaemia homeobox 1 (PBX1) participates in maintaining the pluripotency of human embryonic and haematopoietic stem cells. Our recent studies showed that PBX1 promotes hair follicle-derived mesenchymal stem cell (HF-MSC) proliferation, decreases cellular senescence and apoptosis, and enhances induced pluripotent stem cell generation. Whether PBX1 attenuates HF-MSC senescence and apoptosis by alleviating DNA damage or by enhancing DNA repair remains unknown. In this study, we aimed to determine the effects of PBX1 on the intrinsic ROS or extrinsic HO-induced cellular senescence of HF-MSCs. To this end, we generated HF-MSCs overexpressing either PBX1, or poly (ADP-ribose) polymerase 1, or both. Our results showed that PBX1 overexpression attenuates HF-MSC senescence and apoptosis by alleviating reactive oxygen species (ROS)-mediated DNA damage instead of enhancing DNA repair. This is the first study to report that PBX1 attenuates stem cell senescence and apoptosis by alleviating DNA damage. It provides new insight into the mechanism of stem cell senescence and lays the foundation for the development of strategies for age-related disease prevention and treatment, and in particular, hair follicle repair and regeneration.
在衰老过程中，组织和器官会经历结构退化和功能衰退。DNA损伤被认为是干细胞衰老的主要原因。尽管干细胞发展出了复杂的DNA修复系统，但当内在和外在的损伤超过DNA修复能力时，细胞衰老和与年龄相关的疾病就不可避免地发生了。因此，预防和减轻DNA损伤是在减轻干细胞衰老和预防与年龄相关疾病方面替代DNA修复的一种方法。前B细胞白血病同源框1（PBX1）参与维持人类胚胎干细胞和造血干细胞的多能性。我们最近的研究表明，PBX1促进毛囊来源的间充质干细胞（HF-MSC）增殖，减少细胞衰老和凋亡，并增强诱导多能干细胞的生成。PBX1是通过减轻DNA损伤还是通过增强DNA修复来减轻HF-MSC衰老和凋亡尚不清楚。在本研究中，我们旨在确定PBX1对HF-MSCs内在ROS或外在HO诱导的细胞衰老的影响。为此，我们构建了过表达PBX1、聚（ADP-核糖）聚合酶1或两者的HF-MSCs。我们的结果表明，PBX1过表达通过减轻活性氧（ROS）介导的DNA损伤而非增强DNA修复来减轻HF-MSC衰老和凋亡。这是第一项报道PBX1通过减轻DNA损伤来减轻干细胞衰老和凋亡的研究。它为干细胞衰老机制提供了新的见解，并为与年龄相关疾病的预防和治疗策略，特别是毛囊修复和再生策略的开发奠定了基础。
