Targeting Pancreatic Progenitor Cells in Human Embryonic Stem Cell Differentiation for the Identification of Novel Cell Surface Markers

Bettina Fishman, Hanna Segev, Oded Kopper, Jonathan Nissenbaum, Margarita Schulman, Nissim Benvenisty*, Joseph Itskovitz-Eldor, Danny Kitsberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

New sources of beta cells are needed in order to develop cell therapies for patients with diabetes. An alternative to forced expansion of post-mitotic beta cells is the induction of differentiation of stem-cell derived progenitor cells that have a natural self-expansion capacity into insulin-producing cells. In order to learn more about these progenitor cells at different stages along the differentiation process in which they become progressively more committed to the final beta cell fate, we took the approach of identifying, isolating and characterizing stage specific progenitor cells. We generated human embryonic stem cell (HESC) clones harboring BAC GFP reporter constructs of SOX17, a definitive endoderm marker, and PDX1, a pancreatic marker, and identified subpopulations of GFP expressing cells. Using this approach, we isolated a highly enriched population of pancreatic progenitor cells from hESCs and examined their gene expression with an emphasis on the expression of stage-specific cell surface markers. We were able to identify novel molecules that are involved in the pancreatic differentiation process, as well as stage-specific cell markers that may serve to define (alone or in combination with other markers) a specific pancreatic progenitor cell. These findings may help in optimizing conditions for ultimately generating and isolating beta cells for transplantation therapy.

Original languageAmerican English
Pages (from-to)792-802
Number of pages11
JournalStem Cell Reviews and Reports
Volume8
Issue number3
DOIs
StatePublished - Sep 2012

Bibliographical note

Funding Information:
Acknowledgments We thank Y. Mayshar for his help in chip analysis. This research was supported by grants from JDRF and ESTOOLS.

Keywords

  • BAC-transgenesis
  • GFP
  • GPR-50
  • Genetic labeling
  • Human embryonic stem cells
  • PDX1
  • Pancreatic differentiation
  • SOX17
  • TROP-2

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