Esrrb Complementation Rescues Development of Nanog-Null Germ Cells

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Title: Esrrb Complementation Rescues Development of Nanog-Null Germ Cells
Authors: Zhang, M
Leitch, HG
Tang, WWC
Festuccia, N
Hall-Ponsele, E
Nichols, J
Surani, MA
Smith, A
Chambers, I
Item 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.
Issue Date: 9-Jan-2018
Date of Acceptance: 17-Dec-2017
URI: http://hdl.handle.net/10044/1/62078
DOI: https://dx.doi.org/10.1016/j.celrep.2017.12.060
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/)
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
EMBRYONIC STEM-CELLS
DNA DEMETHYLATION
MOUSE EMBRYOS
SELF-RENEWAL
PLURIPOTENCY
SPECIFICATION
EPIBLAST
NETWORK
CULTURE
MICE
PGCLCs
competence
naive pluripotency
primordial germ cells
transcription factors
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
Online Publication Date: 2018-01-09
Appears in Collections:Clinical Sciences
Imaging Sciences
Molecular Sciences
Faculty of Medicine



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