The dark side of induced pluripotency

Pera, Martin F.

doi:10.1038/471046a

Stem cells

The dark side of induced pluripotency

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Published: 02 March 2011

Volume 471, pages 46–47, (2011)
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Martin F. Pera¹

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Induced pluripotent stem cells have great therapeutic potential. But genomic and epigenomic analyses of these cells generated using current technology reveal abnormalities that may affect their safe use. See Articles p.58, p.63 & p.68

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References

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Martin F. Pera is at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.,
Martin F. Pera

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Martin F. Pera
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Correspondence to Martin F. Pera.

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Pera, M. The dark side of induced pluripotency. Nature 471, 46–47 (2011). https://doi.org/10.1038/471046a

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Published: 02 March 2011
Issue Date: 03 March 2011
DOI: https://doi.org/10.1038/471046a
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Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells

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Editorial Summary

Genetic abnormalities in iPS cells

Epigenomic reprogramming of somatic cells to produce iPS (induced pluripotent stem) cells has important therapeutic potential and is the basis of potentially important disease models. Recent reports that the reprogramming and in vitro culture of iPS cells can induce genetic and epigenetic abnormalities raise concerns over the implications of these abnormalities for clinical applications of iPS cells. Three papers in this issue present genomics studies of human iPS and embryonic stem (ES) cells, and taken together, the results confirm that chromosomal, subchromosomal and single-base level anomalies do accumulate in iPS cells. Hussein et al. compare copy number alterations of early and intermediate passage human iPS cells and report a higher level of copy number variations associated with reprogramming. During moderate length culture, however, iPS cells undergo a selection process leading to a decreased mutation load equivalent to that seen in ES cells. Gore et al. report protein-coding point mutations in 22 human iPS cell lines reprogrammed using five different methods; some mutations were pre-existing in the somatic cells, others were new mutations linked to reprogramming. Lister et al. used whole-genome DNA methylation profiling of human ES, iPS and somatic progenitor cell lines to reveal 'hotspots' in the genomes of iPS cells that are aberrantly reprogrammed.

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The dark side of induced pluripotency

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