Differentiated human stem cells resemble fetal, not adult, β cells

Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic beta cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS+) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS+ cells and (ii) hPSC-derived INS+ (hPSC-INS+) cells more closely resemble human fetal beta cells than adult beta cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS+ cells and true beta cells and provides a catalog of genes whose manipulation may convert hPSC-INS+ cells into functional beta cells.