Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Academic Article uri icon

Overview

MeSH

  • Animals
  • Cell Lineage
  • Gene Expression Regulation
  • Humans
  • Mice
  • Mice, Transgenic
  • Nestin
  • Receptor, Epidermal Growth Factor
  • Signal Transduction
  • Transforming Growth Factor alpha
  • Transgenes

MeSH Major

  • Cell Differentiation
  • Epithelium
  • Intermediate Filament Proteins
  • Metaplasia
  • Nerve Tissue Proteins
  • Pancreas

abstract

  • Epithelial metaplasia occurs when one predominant cell type in a tissue is replaced by another, and is frequently associated with an increased risk of subsequent neoplasia. In both mouse and human pancreas, acinar-to-ductal metaplasia has been implicated in the generation of cancer precursors. We show that pancreatic epithelial explants undergo spontaneous acinar-to-ductal metaplasia in response to EGFR signaling, and that this change in epithelial character is associated with the appearance of nestin-positive transitional cells. Lineage tracing involving Cre/lox-mediated genetic cell labeling reveals that acinar-to-ductal metaplasia represents a true transdifferentiation event, mediated by initial dedifferentiation of mature exocrine cells to generate a population of nestin-positive precursors, similar to those observed during early pancreatic development. These results demonstrate that a latent precursor potential resides within mature exocrine cells, and that this potential is regulated by EGF receptor signaling. In addition, these observations provide a novel example of rigorously documented transdifferentiation within mature mammalian epithelium, and suggest that plasticity of mature cell types may play a role in the generation of neoplastic precursors.

publication date

  • August 2005

has subject area

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Epithelium
  • Gene Expression Regulation
  • Humans
  • Intermediate Filament Proteins
  • Metaplasia
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Nestin
  • Pancreas
  • Receptor, Epidermal Growth Factor
  • Signal Transduction
  • Transforming Growth Factor alpha
  • Transgenes

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1242/dev.01925

PubMed ID

  • 16020518

Additional Document Info

start page

  • 3767

end page

  • 3776

volume

  • 132

number

  • 16