Cell division- and DNA replication-free reprogramming of somatic nuclei for embryonic transcription
Junko Tomikawa,
Christopher A. Penfold,
Takuma Kamiya,
Risa Hibino,
Ayumi Kosaka,
Masayuki Anzai,
Kazuya Matsumoto,
Kei Miyamoto
Affiliations
Junko Tomikawa
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
Christopher A. Penfold
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK; Wellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK
Takuma Kamiya
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
Risa Hibino
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
Ayumi Kosaka
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
Masayuki Anzai
Institute of Advanced Technology, Kindai University, Wakayama 642-0017, Japan
Kazuya Matsumoto
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
Kei Miyamoto
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan; Corresponding author
Summary: Nuclear transfer systems represent the efficient means to reprogram a cell and in theory provide a basis for investigating the development of endangered species. However, conventional nuclear transfer using oocytes of laboratory animals does not allow reprogramming of cross-species nuclei owing to defects in cell divisions and activation of embryonic genes. Here, we show that somatic nuclei transferred into mouse four-cell embryos arrested at the G2/M phase undergo reprogramming toward the embryonic state. Remarkably, genome-wide transcriptional reprogramming is induced within a day, and ZFP281 is important for this replication-free reprogramming. This system further enables transcriptional reprogramming of cells from Oryx dammah, now extinct in the wild. Thus, our findings indicate that arrested mouse embryos are competent to induce intra- and cross-species reprogramming. The direct induction of embryonic transcripts from diverse genomes paves a unique approach for identifying mechanisms of transcriptional reprogramming and genome activation from a diverse range of species.
