Dynamic Changes in the Copy Number of Pluripotency and Cell Proliferation Genes in Human ES and iPS Cells during Reprogramming and Time in Culture

By L. Laurent, Igor Ulitsky, Ileana Slavin, H. Tran, A. Schork, Robert Morey, Candace L. Lynch, Julie V. Harness, Sunray Lee, M. J. Barrero and 15 more. Cell Stem Cell, 2011

914 citations recorded by the source corpus.

Genomic stability is critical for the clinical use of human embryonic and induced pluripotent stem cells. We performed high resolution SNP (single nucleotide polymorphism) analysis on 186 pluripotent and 119 non-pluripotent samples. We report a higher frequency of subchromosomal copy number variations in pluripotent samples compared to non-pluripotent samples, with variations enriched in specific genomic regions. The distribution of these variations differed between hESCs and hiPSCs, characterized by large numbers of duplications found in a few hESC samples and moderate numbers of deletions distributed across many hiPSC samples. For hiPSCs, the reprogramming process was associated with deletions of tumor suppressor genes, while time in culture was associated with duplications of oncogenic genes. We also observed duplications that arose during a differentiation protocol. Our results illustrate the dynamic nature of genomic abnormalities in pluripotent stem cells and the need for frequent genomic monitoring to assure phenotypic stability and clinical safety.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9f585798dd1a4560a924f570a4242d3ed98e3294

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In Molecular Biology

1. Uri Ben‐David
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3. Daisy A. Robinton
4. N. Benvenisty

Citations in the corpus

• Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer (2013, background): “A battery of pluripotency tests performed on human NT-ESCs demonstrated their similarities to genuine IVF-derived ESCs.”
• Generation of isogenic pluripotent stem cells differing exclusively at two early onset Parkinson point mutations (2011, neutral): “It is well established that prolonged culture of hESCs can lead to adaption such as increased growth rate, reduced apoptosis, and the acquisition of chromosomal abnormalities such as copy number variations (CNVs) (Laurent et al., 2011; Närvä et al., 2010).”
• The tumorigenicity of human embryonic and induced pluripotent stem cells (2011, background): “Indeed, a recent study demonstrated a high frequency of subchromosomal gains and deletions in HESCs and HiPSCs, and showed that deleted regions often contain tumour-suppressor genes, and that regions of chromosomal gain contain oncogene”
• Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver (2015, neutral): “These range from chromosomal abnormalities (Laurent et al., 2011),‘‘de novo’’ copy number variations (CNVs) (Hussein et al., 2011), and point mutations in protein-coding regions (Gore et al., 2011).”
• The promise of induced pluripotent stem cells in research and therapy (2012, background): “A comprehensive study by Laurent and colleagues found a higher frequency of subchromosomal CNVs in pluripotent cell samples than in non-pluripotent cell sample”