AI Article Synopsis
- Researchers analyzed 506 human induced pluripotent stem cell (hiPSC) lines generated by the NHLBI's NextGen program to assess their genetic stability.
- Out of these, 149 hiPSC lines showed 258 copy number variations (CNVs) linked to regions associated with cancer-related genes on several chromosomes.
- The study highlights the notable structural instability in specific genomic regions, especially chr20q11.2, which harbors key cancer genes, emphasizing the need for thorough genetic evaluation of hiPSC lines before their application in disease modeling and research.
Article Abstract
Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575060 | PMC |
| http://dx.doi.org/10.1016/j.scr.2020.101803 | DOI Listing |
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