Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors

Kathryn F. Cogger, Ankit Sinha, Farida Sarangi, Emily C. McGaugh, Diane Saunders, Craig Dorrell, Salvador Mejia-Guerrero, Yasaman Aghazadeh, Jillian L. Rourke, Robert A. Screaton, Markus Grompe, Philip R. Streeter, Alvin C. Powers, Marcela Brissova, Thomas Kislinger and M. Cristina Nostro ()
Additional contact information
Kathryn F. Cogger: University Health Network
Ankit Sinha: University of Toronto
Farida Sarangi: University Health Network
Emily C. McGaugh: University Health Network
Diane Saunders: Vanderbilt University
Craig Dorrell: Oregon Health and Science University
Salvador Mejia-Guerrero: University Health Network
Yasaman Aghazadeh: University Health Network
Jillian L. Rourke: Sunnybrook Research Institute
Robert A. Screaton: Sunnybrook Research Institute
Markus Grompe: Oregon Health and Science University
Philip R. Streeter: Oregon Health and Science University
Alvin C. Powers: Vanderbilt University
Marcela Brissova: Vanderbilt University Medical Center
Thomas Kislinger: University of Toronto
M. Cristina Nostro: University Health Network

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract PDX1+/NKX6-1+ pancreatic progenitors (PPs) give rise to endocrine cells both in vitro and in vivo. This cell population can be successfully differentiated from human pluripotent stem cells (hPSCs) and hold the potential to generate an unlimited supply of β cells for diabetes treatment. However, the efficiency of PP generation in vitro is highly variable, negatively impacting reproducibility and validation of in vitro and in vivo studies, and consequently, translation to the clinic. Here, we report the use of a proteomics approach to phenotypically characterize hPSC-derived PPs and distinguish these cells from non-PP populations during differentiation. Our analysis identifies the pancreatic secretory granule membrane major glycoprotein 2 (GP2) as a PP-specific cell surface marker. Remarkably, GP2 is co-expressed with NKX6-1 and PTF1A in human developing pancreata, indicating that it marks the multipotent pancreatic progenitors in vivo. Finally, we show that isolated hPSC-derived GP2+ cells generate β-like cells (C-PEPTIDE+/NKX6-1+) more efficiently compared to GP2− and unsorted populations, underlining the potential therapeutic applications of GP2.

Date: 2017
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DOI: 10.1038/s41467-017-00561-0

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