Reconstitution of the oocyte transcriptional network with transcription factors

Nobuhiko Hamazaki (), Hirohisa Kyogoku, Hiromitsu Araki, Fumihito Miura, Chisako Horikawa, Norio Hamada, So Shimamoto, Orie Hikabe, Kinichi Nakashima, Tomoya S. Kitajima, Takashi Ito, Harry G. Leitch and Katsuhiko Hayashi ()
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Nobuhiko Hamazaki: Kyushu University
Hirohisa Kyogoku: RIKEN Center for Biosystems Dynamics Research
Hiromitsu Araki: Kyushu University
Fumihito Miura: Kyushu University
Chisako Horikawa: Kyushu University
Norio Hamada: Kyushu University
So Shimamoto: Kyushu University
Orie Hikabe: Kyushu University
Kinichi Nakashima: Kyushu University
Tomoya S. Kitajima: RIKEN Center for Biosystems Dynamics Research
Takashi Ito: Kyushu University
Harry G. Leitch: MRC London Institute of Medical Sciences (LMS)
Katsuhiko Hayashi: Kyushu University

Nature, 2021, vol. 589, issue 7841, 264-269

Abstract: Abstract During female germline development, oocytes become a highly specialized cell type and form a maternal cytoplasmic store of crucial factors. Oocyte growth is triggered at the transition from primordial to primary follicle and is accompanied by dynamic changes in gene expression1, but the gene regulatory network that controls oocyte growth remains unknown. Here we identify a set of transcription factors that are sufficient to trigger oocyte growth. By investigation of the changes in gene expression and functional screening using an in vitro mouse oocyte development system, we identified eight transcription factors, each of which was essential for the transition from primordial to primary follicle. Notably, enforced expression of these transcription factors swiftly converted pluripotent stem cells into oocyte-like cells that were competent for fertilization and subsequent cleavage. These transcription-factor-induced oocyte-like cells were formed without specification of primordial germ cells, epigenetic reprogramming or meiosis, and demonstrate that oocyte growth and lineage-specific de novo DNA methylation are separable from the preceding epigenetic reprogramming in primordial germ cells. This study identifies a core set of transcription factors for orchestrating oocyte growth, and provides an alternative source of ooplasm, which is a unique material for reproductive biology and medicine.

Date: 2021
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DOI: 10.1038/s41586-020-3027-9

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