Stochastic fluctuations in gene expression (transcriptional noise), which drive transitions between states, and complex regulatory networks, which define stable interconvertible ‘attractor’ states, are both thought to be involved in the control of stem cell fate. Because population-based studies lack the resolution to reveal the heterogeneity resulting from different attractor states or to uncover their functional significance, on Fiona Watt and colleagues use single-cell gene expression profiling to investigate heterogeneity among human epidermal stem cells. Markers for these cells include the Notch ligand delta-like 1 (DLL1) and the EGFR antagonist LRIG1, but the expression of these proteins is known to vary between cells. The researchers now show that DLL1 expression discriminates between two populations of undifferentiated basal keratinocytes that differ in adhesion and proliferation, and that have distinct transcriptional profiles. These results indicate that intercellular differences in gene expression among human epidermal stem cells cannot be attributed solely to random stochastic fluctuations and suggest that this heterogeneity affects the interaction of these cells with their environment.
