Creating new β cells: cellular transmutation by genomic alchemy

Abstract

To address insulin insufficiency, diabetes research has long focused on techniques for replacing insulin-producing β cells. Studies in mice have suggested that, under some conditions, α cells possess the capacity to transdifferentiate into β cells, although the mechanisms that drive this conversion are unclear. In this issue, Bramswig et al. analyzed the methylation states of purified human α, β, and acinar cells and found α cells exhibit intrinsic phenotypic plasticity associated with specific histone methylation profiles. In addition to expanding our understanding of this potential source of β cells, this compendium of carefully generated human gene expression and epigenomic data in islet cell subtypes constitutes a truly valuable resource for the field.

Figure 1. Asymmetry of β and α cell histone methylation.

In β cells, most β cell–specific genes (e.g., insulin) are monovalently marked as active by histone H3K4me3 (green), whereas α cell–specific genes (e.g., glucagon) are marked as repressed by histone H3K27me3 (red). The converse largely applies to α cells; however, Bramswig et al. show that several genes specifically required for β cell differentiation (e.g., PDX1, MAFA) are bivalently marked in α cells by H3K4me3 and H3K27me3, indicating a paused state with potential for activation. This potential does not appear to apply to α cell development genes in β cells.