Supplementary Material for: Aging-Related Genes in Mesenchymal Stem Cells: A Mini-Review

Adult stem cells in mammalian organs play pivotal roles in the maintenance and repair of these organs throughout the life of the adult and maintain the proper homeostasis of a tissue or organ. Among the adult stem cells described to date, mesenchymal stem cells (MSCs) are highlighted for clinical applications because MSCs have many advantages for cell therapy, including multilineage differentiation, homing, immune modulation and wound-healing effects. However, as the aging of MSCs leads to an age-associated decline in their number and function, it is important to clarify the age-associated factors and regulatory mechanism associated with the MSC aging process.<b> </b>In this review, we amass and discuss the recent data related to age-associated genes in MSCs. In particular, the activities of epigenetic regulatory factors, including histone acetylase and DNA methyltransferase, modulate gene expression and crosstalk with each other during the MSC senescence process. p16^INK4A and high-mobility group A2 play important age-associated roles in the regulation of MSC stemness, and lamin A- and prelamin A-dependent nuclear abnormalities have significant biological relevance in MSC aging. Taken together, the information described here, including the epigenetic regulatory factors, transcription factors and cell signaling, could be used toward the development of treatments for MSC aging and related defects.

哺乳动物器官中的成体干细胞，在成年个体的生命周期中对器官的维持与修复发挥关键作用，并维持组织或器官的正常稳态。在迄今已报道的成体干细胞中，间充质干细胞（mesenchymal stem cells, MSCs）因其在细胞治疗中的诸多优势而备受临床应用关注，这些优势包括多向分化潜能、归巢能力、免疫调节及促伤口愈合效应。然而，间充质干细胞的衰老会导致其数量与功能随年龄增长而下降，因此阐明与间充质干细胞衰老过程相关的年龄关联因素及调控机制具有重要意义。
在本综述中，我们整理并讨论了近年来与MSCs年龄相关基因的研究数据。具体而言，在MSCs衰老过程中，包括组蛋白乙酰转移酶、DNA甲基转移酶在内的表观遗传调控因子的活性可调控基因表达，且彼此间存在相互串扰。p16^INK4A与高迁移率族蛋白A2在调控MSCs干性方面发挥重要的年龄相关作用，而核纤层蛋白A及前核纤层蛋白A介导的核异常与MSCs衰老具有显著的生物学关联。综上，本文所述的表观遗传调控因子、转录因子及细胞信号通路相关信息，可为MSCs衰老及其相关缺陷的治疗手段开发提供参考。