“Recurrent genetic abnormalities in human pluripotent stem cells: definition and routine detection in culture supernatant by targeted droplet digital PCR” by Assou et al.
The unique features of human pluripotent stem cells (hPSCs) open new opportunities for disease modeling, drug discovery and the development of cell-based therapies. However, genetic abnormalities can accumulate during the generation, long-term maintenance or during genome editing of these cells. Therefore, it is crucial to detect these abnormalities as soon as they appear to guaranty the safe and proper use of hPSCs in clinical practice and in research.
To address this issue, Assou et al. performed an exhaustive study by combining data from publications describing the occurrence of hPSC aberrations during in vitro culture. Based on this large meta-analysis, a test called iCS-digital (in culture supernatant-digital PCR) has been designed consisting in a panel of digital PCR probes that target the most recurrent abnormalities identified by these studies.
Thanks to the precision of the digital PCR technology, the iCS-digital test allows the sensitive, precise and absolute quantification of copy number variations (CNVs) and the detection of anomalies that are below the G-banding method resolution, especially the sub-karyotypic 20q11.21 hotspot.
Using the iCS-digital test, Assou et al. could monitor cell integrity through regular screenings, and record the moment where genomic aberrations appeared. Furthermore, the iCS-digital test presents the advantage of using cell culture supernatant instead of intact cells as a DNA source, bypassing the inconvenience of dedicating a certain fraction of cell material for control quality testing.
To conclude, Assou et al. demonstrated the interest of the iCS-digital test for routine hPSC screening, thanks to the simplicity of the collection procedure, the rapidity of the test, and the accuracy of the digital PCR technology. This innovative test can change how hPSC quality control is implemented for their use in basic research, regenerative medicine, and can contribute to secure genome editing workflows.
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