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; M. Cristina Nostro

doi:10.1038/s41467-017-00561-0

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, M. Cristina Nostro

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83 Scopus citations

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.

Original language	English (US)
Article number	331
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00561-0
State	Published - Dec 1 2017

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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10.1038/s41467-017-00561-0

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Cogger, K. F., Sinha, A., Sarangi, F., McGaugh, E. C., Saunders, D., Dorrell, C., Mejia-Guerrero, S., Aghazadeh, Y., Rourke, J. L., Screaton, R. A., Grompe, M., Streeter, P. R., Powers, A. C., Brissova, M., Kislinger, T., & Nostro, M. C. (2017). Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors. Nature communications, 8(1), [331]. https://doi.org/10.1038/s41467-017-00561-0

Cogger, KF, Sinha, A, Sarangi, F, McGaugh, EC, Saunders, D, Dorrell, C, Mejia-Guerrero, S, Aghazadeh, Y, Rourke, JL, Screaton, RA, Grompe, M, Streeter, PR, Powers, AC, Brissova, M, Kislinger, T & Nostro, MC 2017, 'Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors', Nature communications, vol. 8, no. 1, 331. https://doi.org/10.1038/s41467-017-00561-0

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

Abstract

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