Zscan4 restores the developmental potency of embryonic stem cells

Tomokazu Amano, Tetsuya Hirata, Geppino Falco, Manuela Monti, Lioudmila V. Sharova, Misa Amano, Sarah Sheer, Hien G. Hoang, Yulan Piao, Carole A. Stagg, Kohei Yamamizu, Tomohiko Akiyama and Minoru S. H. Ko ()
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Tomokazu Amano: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Tetsuya Hirata: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Geppino Falco: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Manuela Monti: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Lioudmila V. Sharova: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Misa Amano: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Sarah Sheer: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Hien G. Hoang: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Yulan Piao: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Carole A. Stagg: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Kohei Yamamizu: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Tomohiko Akiyama: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH
Minoru S. H. Ko: Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, NIH

Nature Communications, 2013, vol. 4, issue 1, 1-10

Abstract: Abstract The developmental potency of mouse embryonic stem (ES) cells, which is the ability to contribute to a whole embryo, is known to deteriorate during long-term cell culture. Previously, we have shown that ES cells oscillate between Zscan4− and Zscan4+ states, and the transient activation of Zscan4 is required for the maintenance of telomeres and genome stability of ES cells. Here we show that increasing the frequency of Zscan4 activation in mouse ES cells restores and maintains their developmental potency in long-term cell culture. Injection of a single ES cell with such increased potency into a tetraploid blastocyst gives rise to an entire embryo with a higher success rate. These results not only provide a means to rejuvenate ES cells by manipulating Zscan4 expression, but also indicate the active roles of Zscan4 in the long-term maintenance of ES cell potency.

Date: 2013
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DOI: 10.1038/ncomms2966

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