Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates

Anna L. Means, Ingrid M. Meszoely, Kazufumi Suzuki, Yoshiharu Miyamoto, Anil K. Rustgi, Robert J. Coffey, Christopher V E Wright, Doris A. Stoffers, Steven D. Leach

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3767-3776
Number of pages10
JournalDevelopment
Volume132
Issue number16
DOIs
StatePublished - Aug 2005

Fingerprint

Cell Transdifferentiation
Nestin
Acinar Cells
Metaplasia
Epidermal Growth Factor Receptor
Pancreas
Neoplasms
Epithelium
Population

Keywords

  • Cancer
  • Differentiation
  • Metaplasia
  • Mouse
  • Pancreas
  • Stem cells
  • TGFα
  • Transdifferentiation

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Means, A. L., Meszoely, I. M., Suzuki, K., Miyamoto, Y., Rustgi, A. K., Coffey, R. J., ... Leach, S. D. (2005). Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Development, 132(16), 3767-3776. https://doi.org/10.1242/dev.01925

Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. / Means, Anna L.; Meszoely, Ingrid M.; Suzuki, Kazufumi; Miyamoto, Yoshiharu; Rustgi, Anil K.; Coffey, Robert J.; Wright, Christopher V E; Stoffers, Doris A.; Leach, Steven D.

In: Development, Vol. 132, No. 16, 08.2005, p. 3767-3776.

Research output: Contribution to journalArticle

Means, AL, Meszoely, IM, Suzuki, K, Miyamoto, Y, Rustgi, AK, Coffey, RJ, Wright, CVE, Stoffers, DA & Leach, SD 2005, 'Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates', Development, vol. 132, no. 16, pp. 3767-3776. https://doi.org/10.1242/dev.01925
Means, Anna L. ; Meszoely, Ingrid M. ; Suzuki, Kazufumi ; Miyamoto, Yoshiharu ; Rustgi, Anil K. ; Coffey, Robert J. ; Wright, Christopher V E ; Stoffers, Doris A. ; Leach, Steven D. / Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. In: Development. 2005 ; Vol. 132, No. 16. pp. 3767-3776.
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