Cell Stem Cell 10: 583–594
Embryonic stem cells (ESCs) can maintain their undifferentiated state indefinitely in culture (self-renewal), but must also retain the ability to differentiate into the various cell types found in the body (pluripotency). The co-existence of these two properties requires a balance between stable maintenance of ESC identity and the flexibility to reprogram cellular identity upon receiving a differentiation signal. The mechanisms underlying this developmental flexibility are largely unknown. Recently, Reynolds et al (2012) demonstrated that the Nucleosome Remodelling and Deacetylation (NURD) complex helps to maintain the developmental potency of ESCs by enforcing variability in the expression of transcription factors (TFs) that favour self-renewal, resulting in a low-expressing subpopulation of cells that are primed for differentiation. Thus, maintenance of ESC TFs at adequate, but not excessive, levels is important for maintaining ESC pluripotency.