Differentiated human stem cells resemble fetal, not adult, β cells
Author(s)Hrvatin, Sinisa; O'Donnell, Charles William; Deng, Francis; Millman, Jeffrey R.; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K.; Melton, Douglas A.; ... Show more Show less
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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[superscript +]) 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[superscript +] cells and (ii) hPSC-derived INS[superscript +] (hPSC-INS[superscript +]) 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[superscript +] cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS[superscript +] cells into functional β cells.
DepartmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
Hrvatin, S., C. W. O’Donnell, F. Deng, J. R. Millman, F. W. Pagliuca, P. DiIorio, A. Rezania, D. K. Gifford, and D. A. Melton. “Differentiated Human Stem Cells Resemble Fetal, Not Adult, β Cells.” Proceedings of the National Academy of Sciences 111, no. 8 (February 10, 2014): 3038–3043.
Final published version