Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells

Abstract

We have observed karyotypic changes involving the gain of chromosome 17q in three independent human embryonic stem (hES) cell lines on five independent occasions. A gain of chromosome 12 was seen occasionally. This implies that increased dosage of chromosome 17q and 12 gene(s) provides a selective advantage for the propagation of undifferentiated hES cells. These observations are instructive for the future application of hES cells in transplantation therapies in which the use of aneuploid cells could be detrimental.

Concise Review: Induced Pluripotent Stem Cells Versus Embryonic Stem Cells: Close Enough or Yet Too Far Apart?

“…Mutations could bring certain advantages for the change of cell fate, thus representing a strong mutagenic factor. Subsequent proliferation and adaptation to the in vitro culture conditions is another important cause of mutations, although common for other cell lines too, including the ESC where gross mutations have already been noted [73][74][75].…”

Screening of human pluripotent stem cells using CGH and FISH reveals low-grade mosaic aneuploidy and a recurrent amplification of chromosome 1q

“…Significant difference was found in our research between monosomy and trisomy rate, suggesting that chromosome loss is more common. Prior studies highlighted chromosomes 12, 17, 20 and X as involved in most of the genomic aberrations 12,13 and both chromosomal gains and losses were frequently reported in cells from different sources. It is notable that, trisomy 12 is known to take over the culture in a few passages 15,34 but in our study, aneuploid cells carrying additional copy of chromosome 12 do not seem to be enriched in culture over time.…”

“…11 Karyotypic abnormalities of hESCs in long-term cultures have been reported before. [12][13][14][15] In hESCs, most of the alteration have been attributed to chromosomes 12 and 17, but chromosomes X and 20 were also repeatedly described. 12,16 G-banding technique is extremely laborious, requires dividing cells in culture and metaphases of sufficient quality for analysis, which have already proven difficulties to obtain.…”

Les cellules souches embryonnaires humaines révèlent l’existence d’une région hautement instable du génome

“…Dès 2004, plusieurs études ont démontré que les conditions de culture classiques des cellules ES humaines in vitro permettant le maintien de leur état indifférencié, induisaient de façon non négligeable une instabilité chromosomique. Des trisomies des chromosomes 12, 17 ou X ont ainsi été mises en évidence très fréquemment [2,3]. L'hypothèse qui prévaut actuellement pour expliquer ce phénomène est que l'amplification de certains gènes portés par ces chromosomes confère un avantage sélec-tif aux cellules souches indifférenciées.…”