Heterogeneity of SOX9 and HNF1β in Pancreatic Ducts Is Dynamic

Stem Cell Reports. 2018 Mar 13;10(3):725-738. doi: 10.1016/j.stemcr.2018.01.028. Epub 2018 Mar 1.

Abstract

Pancreatic duct epithelial cells have been suggested as a source of progenitors for pancreatic growth and regeneration. However, genetic lineage-tracing experiments with pancreatic duct-specific Cre expression have given conflicting results. Using immunofluorescence and flow cytometry, we show heterogeneous expression of both HNF1β and SOX9 in adult human and murine ductal epithelium. Their expression was dynamic and diminished significantly after induced replication. Purified pancreatic duct cells formed organoid structures in 3D culture, and heterogeneity of expression of Hnf1β and Sox9 was maintained even after passaging. Using antibodies against a second cell surface molecule CD51 (human) or CD24 (mouse), we could isolate living subpopulations of duct cells enriched for high or low expression of HNF1β and SOX9. Only the CD24high (Hnfβhigh/Sox9high) subpopulation was able to form organoids.

Keywords: heterogeneity; organoid; pancreatic ductal cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • CD24 Antigen / metabolism
  • Epithelial Cells / metabolism
  • Hepatocyte Nuclear Factor 1-beta / metabolism*
  • Humans
  • Integrin alphaV / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Organoids / metabolism
  • Pancreatic Ducts / metabolism*
  • SOX9 Transcription Factor / metabolism*

Substances

  • CD24 Antigen
  • HNF1B protein, human
  • Integrin alphaV
  • SOX9 Transcription Factor
  • SOX9 protein, human
  • Hepatocyte Nuclear Factor 1-beta