Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells.
Bottom Line: Moreover, Esrrb can reprogram Nanog(-/-) EpiSCs and can rescue stalled reprogramming in Nanog(-/-) pre-iPSCs.Finally, Esrrb deletion abolishes the defining ability of Nanog to confer LIF-independent ESC self-renewal.These findings are consistent with the functional placement of Esrrb downstream of Nanog.
Affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, Scotland.Show MeSH
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Mentions: To determine the requirement of Esrrb in ESC self-renewal, cells homozygous for a conditional Esrrb knockout allele (Esrrbf/fn) (Chen and Nathans, 2007) and expressing Cre-ERT2 were generated (Figures 7A, S7A, and S7B). Tamoxifen treatment of Esrrbf/fn cells increases the degree of differentiation in these cultures. Nonetheless, stable EsrrbΔ/Δ cell lines genetically devoid of Esrrb were readily isolated (Figure S7C and S7D). Although they show an impaired ability to self-renew in clonal assays (Figure 7C), EsrrbΔ/Δ cells can be propagated in FCS/LIF/GMEMβ and maintain Oct4 expression (Figure 7B). These results establish the fact that despite having a clear stimulatory effect on the efficiency of colony formation, Esrrb is formally dispensable for ESC self-renewal.
Affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, Scotland.