Lysine-specific demethylase 1 inhibitors prevent teratoma development from human induced pluripotent stem cells

Oncotarget
Naoki OsadaYusuke Furukawa

Abstract

Human induced pluripotent stem cells (hiPSCs) are creating great expectations for regenerative medicine. However, safety strategies must be put in place to guard against teratoma formation after transplantation of hiPSC-derived cells into patients. Recent studies indicate that epigenetic regulators act at the initial step of tumorigenesis. Using gain-of-function and loss-of-function approaches, we show here that the expression and function of lysine-specific demethylase 1 (LSD1) are tightly regulated in hiPSCs, and their deregulation underlies the development of teratomas. Consistent with these results, we demonstrate that an LSD1 inhibitor, S2157, prevented teratoma formation from hiPSCs transplanted into immunodeficient mice. This novel action of LSD1 and the effects of its inhibition potentially allow for the development of new clinical applications and therapeutic strategies using hiPSCs.

References

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Oct 12, 2017·Cell Reports·Masahito YoshiharaYasuhiro Murakawa

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Citations

Mar 15, 2019·Stem Cell Research & Therapy·Jolanta GoreckaAlan Dardik
Aug 15, 2019·Biochemical and Biophysical Research Communications·Jiro KikuchiYusuke Furukawa
Nov 18, 2021·Bioengineered·Li ZengSheng-Kang Luo

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Methods Mentioned

BETA
genetic modification
FCS
PCR

Software Mentioned

IVIS Imaging System
Living Image
Prism

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