Esrrb Complementation Rescues Development of Nanog-Null Germ Cells
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a positively regulated direct target of NANOG in ESCs that can substitute qualitatively for Nanog function in ESCs. Whether this functional substitution extends to the germline is unknown. Here, we show that germline deletion of Nanog reduces PGC numbers 5-fold at midgestation. Despite this quantitative depletion, Nanog-null PGCs can complete germline development in contrast to previous findings. PGC-like cell (PGCLC) differentiation of Nanog-null ESCs is also impaired, with Nanog-null PGCLCs showing decreased proliferation and increased apoptosis. However, induced expression of Esrrb restores PGCLC numbers as efficiently as Nanog. These effects are recapitulated in vivo: knockin of Esrrb to Nanog restores PGC numbers to wild-type levels and results in fertile adult mice. These findings demonstrate that Esrrb can replace Nanog function in germ cells.
Date Issued
2018-01-09
Date Acceptance
2017-12-17
Citation
CELL REPORTS, 2018, 22 (2), pp.332-339
ISSN
2211-1247
Publisher
CELL PRESS
Start Page
332
End Page
339
Journal / Book Title
CELL REPORTS
Volume
22
Issue
2
Copyright Statement
© 2017 The Author(s). Open Access under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/)
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000419587900003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
EMBRYONIC STEM-CELLS
DNA DEMETHYLATION
MOUSE EMBRYOS
SELF-RENEWAL
PLURIPOTENCY
SPECIFICATION
EPIBLAST
NETWORK
CULTURE
MICE
Publication Status
Published
Date Publish Online
2018-01-09