TY - JOUR
T1 - Differentiated human stem cells resemble fetal, not adult, β cells
AU - Hrvatin, Siniša
AU - O'Donnell, Charles W.
AU - Deng, Francis
AU - Millman, Jeffrey R.
AU - Pagliuca, Felicia Walton
AU - DiIorio, Philip
AU - Rezania, Alireza
AU - Gifford, David K.
AU - Melton, Douglas A.
PY - 2014/2/25
Y1 - 2014/2/25
N2 - 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.
AB - 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.
KW - Beta cells
KW - Differentiation
KW - MARIS
KW - Transcriptional profiling
UR - http://www.scopus.com/inward/record.url?scp=84896889356&partnerID=8YFLogxK
U2 - 10.1073/pnas.1400709111
DO - 10.1073/pnas.1400709111
M3 - Article
C2 - 24516164
AN - SCOPUS:84896889356
SN - 0027-8424
VL - 111
SP - 3038
EP - 3043
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -