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Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.

Published version
Peer-reviewed

Type

Article

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Authors

Zhang, Man 
Leitch, Harry G 
Tang, Walfred WC 
Festuccia, Nicola 
Hall-Ponsele, Elisa 

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.

Description

Keywords

PGCLCs, competence, naive pluripotency, primordial germ cells, transcription factors, Animals, Cell Differentiation, Germ Cells, Mice, Nanog Homeobox Protein, Receptors, Estrogen

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

22

Publisher

Elsevier BV