Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.

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

Role of Sox2 in preimplantation and postimplantation pluripotency

Microarray gene expression analysis of mouse embryonic stem cells in different culture conditions. 4 conditions: AFN=Activin/FGF/N2B27 (unsorted (All) or sorted by Sox2 expression into High or Low), PCLN=LIF/2i/N2B27, LBN=LIF/BMP/N2B27 (sorted by Sox2 expression into High and Low) and FCSL=LIF/FCS/GMEM (sorted by Sox2 expression into High and Low). 3 replicates per group. 24 samples total.Sox2 is a key transcription factor directing embryonic stem cell (ESC) pluripotency. However, the role of SoxB1 proteins in epiblast stem cell (EpiSC) pluripotency is unknown. Here we compare the transcriptomes of pluripotent cells cultured in different conditions that express different levels of Sox2. While highest Sox2 level in ESCs are enriched for naive pluripotency markers, ESCs and EpiSCs expressing the same Sox2 level were transcriptionally distinct. Thus Sox2 levels do not dictate the distinction between ESC and EpiSC states.Corsinotti A, Wong FC, Tatar T, Szczerbinska I et al. Distinct SoxB1 networks are required for naïve and primed pluripotency. Elife 2017 Dec 19;6. PMID: 2925686