Embryonic stem cell (ESC) cultures display a marked heterogeneity in the expression of Nanog, one of several core pluripotency factors required for proper development in vivo. In addition, Nanog levels have also been shown to fluctuate in individual ESCs in vitro; however, the extent and functional consequences of these fluctuations in different pluripotency states has not been fully established. Now, on p. , Domingos Henrique and colleagues take a closer look at Nanog expression in mouse (m) ESCs grown in both 2i/LIF and serum/LIF conditions, which promote naïve versus primed pluripotency states, respectively. Using confocal time-lapse imaging of individual Nanog-reporting mESCs, the authors show that the amplitude of Nanog fluctuation in individual mESCs is similar regardless of culture conditions. The authors also show that divergent Nanog levels exist even between sister cells, and that Nanog levels do not correlate in any way to the cell cycle. In both conditions, cells that expressed low levels of Nanog showed decreased clonogenic capacity and increased lineage priming, whereas the opposite was true when high levels of Nanog were observed. The authors conclude that fluctuating Nanog expression is a cell-intrinsic property that allows ESCs to explore available lineage options in the pluripotent space.
