Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.

Man Zhang, Harry G Leitch, Walfred W C Tang, Nicola Festuccia, Elisa Hall-Ponsele, Jennifer Nichols, M Azim Surani, Austin Smith, Ian Chambers

Cell reports 2018 Jan 09

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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. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Man Zhang, Harry G Leitch, Walfred W C Tang, Nicola Festuccia, Elisa Hall-Ponsele, Jennifer Nichols, M Azim Surani, Austin Smith, Ian Chambers. Esrrb Complementation Rescues Development of Nanog-Null Germ Cells. Cell reports. 2018 Jan 09;22(2):332-339