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Chromosome dynamic changes in two cultured Chinese human embryonic stem cell lines: single nucleotide polymorphism, copy number variation and loss of heterozygosity. | LitMetric

AI Article Synopsis

  • - The stability of genes in human embryonic stem cells (hESCs) is crucial for clinical applications, and a study analyzed two Chinese hESC lines (Zh1 and Zh21) over different passage numbers to assess this stability.
  • - Findings revealed that while early passages showed relative gene stability, increased passage numbers resulted in significant gene instability, with observed copy number variations (CNVs) in both cell lines and a normal Chinese population.
  • - To ensure hESC safety, the study recommends adopting high-resolution DNA analysis, monitoring chromosomal properties more frequently as passage numbers increase, and observing the pathways of mutant genes since they may affect cell functions.

Article Abstract

The quality and safety of human embryonic stem cells (hESCs) in clinical application depend on gene stability. Two Chinese hESC lines, Zh1 and Zh21, were incubated over a long period. We observed and compared the gene stability in the passage numbers 20, 17 for Zh1 cell line and passage numbers 27, 60, 68 for Zh21 cell line. Single nucleotide polymorphisis analysis indicated that hESCs in early passages had relative gene stability; and with the increase in passage number, gene instability became strong. We also found that there were copy number variations (CNVs) in both Zh21 and Zh1. We analyzed the CNVs of Chinese Han Beijing man (CHB; normal Chinese people) and found that the all CNV forms were the loss in Zh21, Zh1, and CHB. We also analyzed and compared the related pathways of the mutant genes. We propose three steps to ensure hESC safety. Firstly, besides the conventional methods such as pluripotent genes, chromosome G-banding and teratoma, high-resolution DNA chip analysis should also be adopted; secondly, chromosomal properties are monitored every 10 passages in less than passage 50 and every 5 passages in more than passage 50; thirdly, the related pathways of mutant genes should be observed because only the mutant genes with variations of their related pathways may affected cell functions.

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Source
http://dx.doi.org/10.1002/jcb.24229DOI Listing

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