Long non-coding RNAs (lncRNAs) have been shown to modulate pluripotency and lineage commitment in embryonic stem cells, but their role in homeostasis has not been explored in detail.

Khavari and colleagues (Genes Dev. http://doi.org/hp6; 2012) have used high-throughput transcriptome sequencing and tiling arrays to survey the non-coding RNAs expressed in human progenitors and differentiated cells for several cell types, including keratinocytes, adipocytes and osteoblasts. They have identified an 855-base-pair non-coding RNA (named ANCR) that is greatly downregulated during differentiation. The authors observed that depletion of ANCR using RNAi in primary human keratinocytes induces the expression of genes associated with epidermal differentiation, including key transcription factors. However, the overall expression program affected by ANCR is wider than just these target transcription factor genes. The genes affected by ANCR loss are located throughout the genome, indicating a mode of action different from that reported for other lncRNAs, which are suggested to act on enhancers of proximal genes.

The authors also examined the effect of depleting ANCR in a human skin organotypic assay that recapitulates the stratified organization observed in vivo, with undifferentiated cells located near a basement membrane and cells becoming progressively more differentiated towards the surface. They observed the expression of genes normally associated with terminal differentiation in the most basal layer. Further studies will unravel the mode of regulation and action of ANCR in maintaining a progenitor state.