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 β 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 β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS⁺ cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS⁺ cells into functional β cells.