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Title: Prospectively Isolated NGN3-Expressing Progenitors From Human Embryonic Stem Cells Give Rise to Pancreatic Endocrine Cells
Authors: Cai, Qing ×
Bonfanti, Paola
Sambathkumar, Rangarajan
Vanuytsel, Kim
Vanhove, Jolien
Gysemans, Conny
Debiec-Rychter, Maria
Raitano, Susanna
Heimberg, Harry
Ordovas Vidal, Laura
Verfaillie, Catherine #
Issue Date: Apr-2014
Publisher: AlphaMed Press, Inc
Series Title: Stem Cells Translational Medicine vol:3 issue:4 pages:489-499
Abstract: Pancreatic endocrine progenitors obtained from human embryonic stem cells (hESCs) represent a promising source to develop cell-based therapies for diabetes. Although endocrine pancreas progenitor cells have been isolated from mouse pancreata on the basis of Ngn3 expression, human endocrine progenitors have not been isolated yet. As substantial differences exist between human and murine pancreas biology, we investigated whether it is possible to isolate pancreatic endocrine progenitors from differentiating hESC cultures by lineage tracing of NGN3. We targeted the 3' end of NGN3 using zinc finger nuclease-mediated homologous recombination to allow selection of NGN3eGFP(+) cells without disrupting the coding sequence of the gene. Isolated NGN3eGFP(+) cells express PDX1, NKX6.1, and chromogranin A and differentiate in vivo toward insulin, glucagon, and somatostatin single hormone-expressing cells but not to ductal or exocrine pancreatic cells or other endodermal, mesodermal, or ectodermal lineages. This confirms that NGN3(+) cells represent pancreatic endocrine progenitors in humans. In addition, this hESC reporter line constitutes a unique tool that may aid in gaining insight into the developmental mechanisms underlying fate choices in human pancreas and in developing cell-based therapies.
URI: 
ISSN: 2157-6564
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdepartemental Stem Cell Institute (-)
Department of Human Genetics - miscellaneous
Stem Cell Biology and Embryology (+)
× corresponding author
# (joint) last author

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