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Chromosomal aberrations after induced pluripotent stem cells reprogramming.
Genetics and Molecular Biology ( IF 1.7 ) Pub Date : 2021-09-03 , DOI: 10.1590/1678-4685-gmb-2020-0147
Isadora May Vaz 1, 2 , Tamara Borgonovo 1, 2 , Tais Hanae Kasai-Brunswick 3, 4 , Danúbia Silva Dos Santos 3 , Fernanda Cristina Paccola Mesquita 3 , Juliana Ferreira Vasques 2, 3 , Fernanda Gubert 2, 5 , Carmen Lúcia Kuniyoshi Rebelatto 1, 2 , Alexandra Cristina Senegaglia 1, 2 , Paulo Roberto Slud Brofman 1, 2
Affiliation  

Induced pluripotent stem cells (iPSCs) are generated from adult cells that have been reprogrammed to pluripotency. However, in vitro cultivation and genetic reprogramming increase genetic instability, which could result in chromosomal abnormalities. Maintenance of genetic stability after reprogramming is required for possible experimental and clinical applications. The aim of this study was to analyze chromosomal alterations by using the G-banding karyotyping method applied to 97 samples from 38 iPSC cell lines generated from peripheral blood or Wharton's jelly. Samples from patients with long QT syndrome, Jervell and Lange-Nielsen syndrome and amyotrophic lateral sclerosis and from normal individuals revealed the following chromosomal alterations: acentric fragments, chromosomal fusions, premature centromere divisions, double minutes, radial figures, ring chromosomes, polyploidies, inversions and trisomies. An analysis of two samples generated from Wharton's jelly before and after reprogramming showed that abnormal clones can emerge or be selected and generate an altered lineage. IPSC lines may show clonal and nonclonal chromosomal aberrations in several passages (from P6 to P34), but these aberrations are more common in later passages. Many important chromosomal aberrations were detected, showing that G-banding is very useful for evaluating genetic instability with important repercussions for the application of iPSC lines.

中文翻译:

诱导多能干细胞重编程后的染色体畸变。

诱导多能干细胞 (iPSC) 是从已重新编程为多能性的成体细胞中产生的。然而,体外培养和基因重编程增加了遗传不稳定性,这可能导致染色体异常。可能的实验和临床应用需要重编程后维持遗传稳定性。本研究的目的是使用 G 显带核型分析方法分析染色体改变,该方法适用于来自外周血或沃顿氏胶产生的 38 个 iPSC 细胞系的 97 个样本。来自长 QT 综合征、Jervell 和 Lange-Nielsen 综合征以及肌萎缩侧索硬化患者和正常个体的样本显示以下染色体改变:无着丝粒片段、染色体融合、过早着丝粒分裂、双分钟、放射状图形、环状染色体、多倍体、倒位和三体。对重编程前后沃顿氏果冻产生的两个样本的分析表明,异常克隆可以出现或被选择并产生改变的谱系。IPSC 系可能在几个传代(从 P6 到 P34)中显示克隆和非克隆染色体畸变,但这些畸变在以后的传代中更为常见。检测到许多重要的染色体畸变,表明 G 带对于评估遗传不稳定性非常有用,对 iPSC 系的应用具有重要影响。IPSC 系可能在几个传代(从 P6 到 P34)中显示克隆和非克隆染色体畸变,但这些畸变在以后的传代中更为常见。检测到许多重要的染色体畸变,表明 G 带对于评估遗传不稳定性非常有用,对 iPSC 系的应用具有重要影响。IPSC 系可能在几个传代(从 P6 到 P34)中显示克隆和非克隆染色体畸变,但这些畸变在以后的传代中更为常见。检测到许多重要的染色体畸变,表明 G 带对于评估遗传不稳定性非常有用,对 iPSC 系的应用具有重要影响。
更新日期:2021-09-03
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