Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells

Tetsuya Hirata; Tomokazu Amano; Yuhki Nakatake; Misa Amano; Yulan Piao; Hien G. Hoang; Minoru S.H. Ko

doi:10.1038/srep00208

Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells

Tetsuya Hirata, Tomokazu Amano, Yuhki Nakatake, Misa Amano, Yulan Piao, Hien G. Hoang, Minoru S.H. Ko

Research output: Contribution to journal › Article › peer-review

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Abstract

The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in 2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required only for the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.

Original language	English
Article number	208
Journal	Scientific reports
Volume	2
DOIs	https://doi.org/10.1038/srep00208
Publication status	Published - 2012
Externally published	Yes

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title = "Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells",

abstract = "The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in 2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required only for the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.",

author = "Tetsuya Hirata and Tomokazu Amano and Yuhki Nakatake and Misa Amano and Yulan Piao and Hoang, {Hien G.} and Ko, {Minoru S.H.}",

note = "Funding Information: We thank Hong Yu, Carole Stagg, Yong Qian, and Dawood Dudekula for technical assistance. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.",

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AU - Hirata, Tetsuya

AU - Amano, Tomokazu

AU - Nakatake, Yuhki

AU - Amano, Misa

AU - Piao, Yulan

AU - Hoang, Hien G.

AU - Ko, Minoru S.H.

N1 - Funding Information: We thank Hong Yu, Carole Stagg, Yong Qian, and Dawood Dudekula for technical assistance. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.

PY - 2012

Y1 - 2012

N2 - The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in 2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required only for the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.

AB - The generation of induced pluripotent stem cells (iPSCs) by the forced expression of defined transcription factors in somatic cells holds great promise for the future of regenerative medicine. However, the initial reprogramming mechanism is still poorly understood. Here we show that Zscan4, expressed transiently in 2-cell embryos and embryonic stem cells (ESCs), efficiently produces iPSCs from mouse embryo fibroblasts when coexpressed with Klf4, Oct4, and Sox2. Interestingly, the forced expression of Zscan4 is required only for the first few days of iPSC formation. Microarray analysis revealed transient and early induction of preimplantation-specific genes in a Zscan4-dependent manner. Our work indicates that Zscan4 is a previously unidentified potent natural factor that facilitates the reprogramming process and reactivates early embryonic genes.

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Zscan4 transiently reactivates early embryonic genes during the generation of induced pluripotent stem cells

Abstract

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