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So how different are they? - New Analyses show the Equivalence of Karyotypic Abnormalities in iPSC and ESC



From Nature Biotechnology.

Recent correspondence in Nature Biotechnology has suggested that there are no notable differences in the incidence of chromosomal aberrations between ESC and iPSC. The paper (Taapken et al) from Karen D Montgomery of the WiCell Research Institute in Wisconsin analysed 552 cultures of 219 human iPSC lines and 1,163 cultures from 40 human ESC lines from 97 investigators in 29 laboratories - no mean feat. Their analysis showed that 12.5% of the iPSC lines had an abnormal karyotype while the figure in the ESC lines was 12.9%.This wide study is generally at odds with multiple recent publications (See Genetic Instability in Induced Pluripotent Stem Cells: One Step Forward in Understanding, Two Steps Back from the Clinic?).

Further this situation is reminiscent of studies into the similarity/dissimilarity of epigenetic modifications in mouse and human ESC and iPSC. Multiple studies had reported that patterns of epigenetic modifications were distinct between iPSC and ESC, while a later report suggested similarity between the two cell types (Guenther et al). Interestingly, one report which studied the differences in gene expression from multiple sources, suggested that some of the reported differences between ESC and iPSC were laboratory specific and perhaps did not reflect actual differences between iPSC and ESC (Newman and Cooper). Such differences could be due to culture conditions, method of reprogramming, somatic cell of origin or variances in statistical analyses.

Multiple papers in high impact journals have been asking the same question for a long time now: Are iPSC and ESC equivalent? Analysis of gene expression, histone and DNA modification and now genetic stability has led to the publication of a great deal of data, but with no clear answer. Perhaps the real test of the usefulness of iPSC will be in the study of differentiated cells/tissues from these cells and their long term functionality.



Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells.
Taapken SM, Nisler BS, Newton MA, Sampsell-Barron TL, Leonhard KA, McIntire EM, Montgomery KD.
Nat Biotechnol. 2011 Apr;29(4):313-4.

Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells.
Guenther MG, Frampton GM, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R, Young RA.
Cell Stem Cell. 2010 Aug 6;7(2):249-57.

Lab-specific gene expression signatures in pluripotent stem cells.
Newman AM, Cooper JB.
Cell Stem Cell. 2010 Aug 6;7(2):258-62.