Comprehensive characterization of genomic instability in pluripotent stem cells and their derived neuroprogenitor cell lines

The genomic integrity of two human pluripotent stem cells and their derived neuroprogenitor cell lines was studied, applying a combination of high-resolution genetic methodologies. The usefulness of combining array-comparative genomic hybridization (aCGH) and multiplex fluorescence in situ hybridization (M-FISH) techniques should be delineated to exclude/detect a maximum of possible genomic structural aberrations. Interestingly, in parts different genomic imbalances at chromosomal and subchromosomal levels were detected in pluripotent stem cells and their derivatives. Some of the copy number variations were inherited from the original cell line, whereas other modifications were presumably acquired during the differentiation and manipulation procedures. These results underline the necessity to study both pluripotent stem cells and their differentiated progeny by as many approaches as possible in order to assess their genomic stability before using them in clinical therapies.

► 14 CNV in two human pluripotent neuroprogenitor-cell-lines and their originals were identified.
► One copy number variant (CNV) in 20q was confirmed to be a recurrent imbalance in stem cells.
► CNVs can be inherited from the original source of pluripotent cells or develop during cultivation.
► Chromosomally stable stem cell lines need to be checked in more detail prior use in human therapy.