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

Siniša Hrvatin, Charles W. O'Donnell, Francis Deng, Jeffrey R. Millman, Felicia Walton Pagliuca, Philip DiIorio, Alireza Rezania, David K. Gifford, Douglas A. Melton

Research output: Contribution to journalArticlepeer-review

194 Scopus citations


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.

Original languageEnglish
Pages (from-to)3038-3043
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 25 2014


  • Beta cells
  • Differentiation
  • Transcriptional profiling


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