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

Author

Listed:
  • Kathryn F. Cogger

    (University Health Network
    University Health Network)

  • Ankit Sinha

    (University of Toronto)

  • Farida Sarangi

    (University Health Network
    University Health Network)

  • Emily C. McGaugh

    (University Health Network
    University Health Network
    University of Toronto)

  • Diane Saunders

    (Vanderbilt University)

  • Craig Dorrell

    (Oregon Health and Science University)

  • Salvador Mejia-Guerrero

    (University Health Network)

  • Yasaman Aghazadeh

    (University Health Network
    University Health Network)

  • Jillian L. Rourke

    (Sunnybrook Research Institute)

  • Robert A. Screaton

    (Sunnybrook Research Institute
    University of Toronto)

  • Markus Grompe

    (Oregon Health and Science University)

  • Philip R. Streeter

    (Oregon Health and Science University)

  • Alvin C. Powers

    (Vanderbilt University
    VA Tennessee Valley Healthcare System
    Vanderbilt University Medical Center)

  • Marcela Brissova

    (Vanderbilt University Medical Center)

  • Thomas Kislinger

    (University of Toronto
    University Health Network)

  • M. Cristina Nostro

    (University Health Network
    University Health Network
    University of Toronto)

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.

Suggested Citation

  • 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 Gro, 2017. "Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00561-0
    DOI: 10.1038/s41467-017-00561-0
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