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 identify genes controlled by Nanog, we compared the transcriptional profiles of ESCs in which GFP has been knocked in to one of the Nanog alleles (TNG cells; Chambers et al., 2007) that were sorted into SSEA1+/GFPhigh and SSEA1+/GFPlow populations, together with Nanog+/+ and Nanog−/− cells (Chambers et al., 2007) (Figure 1A). Good agreement between duplicate samples of Nanog−/− RNA indicated reliable output from the Deep-SAGE protocols. Moreover, broad agreement was observed between both Nanog−/− and Nanog:GFP− as well as between Nanog+/+ and Nanog:GFP+ cells. Of 500 genes showing the greatest change in expression, Esrrb was the transcription factor that showed the closest positive correlations with Nanog and consistent variations in both Nanog:GFP+ versus Nanog:GFP− and wild-type versus Nanog−/− comparisons (fold change ≥1.5), closely followed by Klf4 (Table S1.1). To better understand the role of Esrrb in ESC pluripotency, we further characterized the expression of the Esrrb gene in ESCs and its regulation by 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.