Institute of Pharmacology and Toxicology, Technische Universität Dresden, Dresden, Germany.
Stem Cells. 2022 Jun 22;40(6):546-555. doi: 10.1093/stmcls/sxac020.
The potential of human induced pluripotent stem cells (iPSCs) to self-renew indefinitely and to differentiate virtually into any cell type in unlimited quantities makes them attractive for in vitro disease modeling, drug screening, personalized medicine, and regenerative therapies. As the genome of iPSCs thoroughly reproduces that of the somatic cells from which they are derived, they may possess genetic abnormalities, which would seriously compromise their utility and safety. Genetic aberrations could be present in donor somatic cells and then transferred during iPSC generation, or they could occur as de novo mutations during reprogramming or prolonged cell culture. Therefore, to warrant the safety of human iPSCs for clinical applications, analysis of genetic integrity, particularly during iPSC generation and differentiation, should be carried out on a regular basis. On the other hand, reprogramming of somatic cells to iPSCs requires profound modifications in the epigenetic landscape. Changes in chromatin structure by DNA methylations and histone tail modifications aim to reset the gene expression pattern of somatic cells to facilitate and establish self-renewal and pluripotency. However, residual epigenetic memory influences the iPSC phenotype, which may affect their application in disease therapeutics. The present review discusses the somatic cell origin, genetic stability, and epigenetic memory of iPSCs and their impact on basic and translational research.
人类诱导多能干细胞（iPSCs）具有无限自我更新和分化为几乎任何细胞类型的潜力，这使得它们在体外疾病建模、药物筛选、个性化医疗和再生疗法中具有吸引力。由于 iPSCs 的基因组完全复制了它们来源的体细胞的基因组，因此它们可能存在遗传异常，这将严重影响它们的实用性和安全性。遗传异常可能存在于供体细胞中，然后在 iPSC 生成过程中转移，也可能在重编程或长期细胞培养过程中作为新出现的突变发生。因此，为了保证人类 iPSCs 在临床应用中的安全性，应定期对遗传完整性进行分析，特别是在 iPSC 生成和分化过程中。另一方面，体细胞重编程为 iPSCs 需要对表观遗传景观进行深刻的修饰。通过 DNA 甲基化和组蛋白尾部修饰改变染色质结构，旨在重置体细胞的基因表达模式，以促进和建立自我更新和多能性。然而，残留的表观遗传记忆会影响 iPSC 的表型，这可能会影响它们在疾病治疗中的应用。本文综述了 iPSCs 的体细胞来源、遗传稳定性和表观遗传记忆及其对基础和转化研究的影响。
