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Curr Opin Genet Dev. 2014 Oct;28:43-9. doi: 10.1016/j.gde.2014.09.008. Epub 2014 Oct 14.

Cancer-like epigenetic derangements of human pluripotent stem cells and their impact on applications in regeneration and repair.

Author information

1
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA.
2
Division of Cancer Biology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA.
3
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21205, USA. Electronic address: ezambid1@jhmi.edu.

Abstract

A growing body of work has raised concern that many human pluripotent stem cell (hPSC) lines possess tumorigenic potential following differentiation to clinically relevant lineages. In this review, we highlight recent work characterizing the spectrum of cancer-like epigenetic derangements in human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) that are associated with reprogramming errors or prolonged culture that may contribute to such tumorigenicity. These aberrations include cancer-like promoter DNA hypermethylation and histone marks associated with pluripotency, as well as aberrant X-chromosome regulation. We also feature recent work that suggests optimized high-fidelity reprogramming derivation methods can minimize cancer-associated epigenetic aberrations in hPSC, and thus ultimately improve the ultimate clinical utility of hiPSC in regenerative medicine.

PMID:
25461449
PMCID:
PMC4262610
DOI:
10.1016/j.gde.2014.09.008
[Indexed for MEDLINE]
Free PMC Article

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