Reconstitution of the oocyte transcriptional network with transcription factors
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Accepted version
Supporting information
Author(s)
Type
Journal Article
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 Issued
2020-12-16
Online Publication Date
2021-06-16T23:01:21Z
Date Acceptance
2020-10-28
ISSN
0028-0836
Publisher
Nature Research
Start Page
264
End Page
269
Journal / Book Title
Nature
Volume
589
Issue
7841
Copyright Statement
© The Author(s), under exclusive licence to Springer Nature Limited 2020. The final publication is available at Springer via https://doi.org/10.1038/s41586-020-3027-9
Identifier
https://www.nature.com/articles/s41586-020-3027-9
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Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GERM-CELL
GENE-EXPRESSION
R-PACKAGE
MOUSE
DIFFERENTIATION
GROWTH
PROGRAM
MEIOSIS
SOHLH1
NOBOX
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GERM-CELL
GENE-EXPRESSION
R-PACKAGE
MOUSE
DIFFERENTIATION
GROWTH
PROGRAM
MEIOSIS
SOHLH1
NOBOX
General Science & Technology
Publication Status
Published
Date Publish Online
2020-12-16