程序性干细胞产品的基因组稳定性。

Genome stability of programmed stem cell products.

机构信息

Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiothoracic, Transplantation and Vascular Surgery, REBIRTH Cluster of Excellence, German Center for Lung Research, Hannover Medical School, Germany.

出版信息

Adv Drug Deliv Rev. 2017 Oct 1;120:108-117. doi: 10.1016/j.addr.2017.09.004. Epub 2017 Sep 13.

DOI:10.1016/j.addr.2017.09.004

PMID:28917518

Abstract

Inherited and acquired genomic abnormalities are known to cause genetic diseases and contribute to cancer formation. Recent studies demonstrated a substantial mutational load in mouse and human embryonic and induced pluripotent stem cells (ESCs and iPSCs). Single nucleotide variants, copy number variations, and larger chromosomal abnormalities may influence the differentiation capacity of pluripotent stem cells and the functionality of their derivatives in disease modeling and drug screening, and are considered a serious risk for cellular therapies based on ESC or iPSC derivatives. This review discusses the types and origins of different genetic abnormalities in pluripotent stem cells, methods for their detection, and the mechanisms of development and enrichment during reprogramming and culture expansion.

摘要

已知遗传和获得性基因组异常可导致遗传疾病，并促成癌症的形成。最近的研究表明，在小鼠和人类胚胎及诱导多能干细胞（ES 细胞和 iPS 细胞）中存在大量的突变负荷。单核苷酸变异、拷贝数变异和更大的染色体异常可能会影响多能干细胞的分化能力及其在疾病建模和药物筛选中的衍生物的功能，并被认为是基于 ESC 或 iPSC 衍生物的细胞治疗的严重风险。本文综述了多能干细胞中不同遗传异常的类型和来源、检测方法，以及在重编程和培养扩增过程中发育和富集的机制。