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

作者:Cogger Kathryn F; Sinha Ankit; Sarangi Farida; McGaugh Emily C; Saunders Diane; Dorrell Craig; Mejia Guerrero Salvador; Aghazadeh Yasaman; Rourke Jillian L; Screaton Robert A; Grompe Markus; Streeter Philip R; Powers Alvin C; Brissova Marcela; Kislinger Thomas; Nostro M Cristina
来源:Nature Communications, 2017, 8(1): 331.
DOI:10.1038/s41467-017-00561-0

摘要

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 beta 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 beta-like cells (C-PEPTIDE+/NKX6-1(+)) more efficiently compared to GP2-and unsorted populations, underlining the potential therapeutic applications of GP2.

  • 出版日期2017-8-24