Transcriptional maintenance of pancreatic acinar identity, differentiation, and homeostasis by PTF1A

Chinh Q. Hoang, Michael A. Hale, Ana C. Azevedo-Pouly, Hans P. Elsässer, Tye G. Deering, Spencer G. Willet, Fong C. Pan, Mark A. Magnuson, Christopher V E Wright, Galvin H. Swift, Raymond J. MacDonald

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Maintenance of cell type identity is crucial for health, yet little is known of the regulation that sustains the long-term stability of differentiated phenotypes. To investigate the roles that key transcriptional regulators play in adult differentiated cells, we examined the effects of depletion of the developmental master regulator PTF1A on the specialized phenotype of the adult pancreatic acinar cell in vivo. Transcriptome sequencing and chromatin immunoprecipitation sequencing results showed that PTF1A maintains the expression of genes for all cellular processes dedicated to the production of the secretory digestive enzymes, a highly attuned surveillance of unfolded proteins, and a heightened unfolded protein response (UPR). Control by PTF1A is direct on target genes and indirect through a ten-member transcription factor network. Depletion of PTF1A causes an imbalance that overwhelms the UPR, induces cellular injury, and provokes acinar metaplasia. Compromised cellular identity occurs by derepression of characteristic stomach genes, some of which are also associated with pancreatic ductal cells. The loss of acinar cell homeostasis, differentiation, and identity is directly relevant to the pathologies of pancreatitis and pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)3033-3047
Number of pages15
JournalMolecular and Cellular Biology
Volume36
Issue number24
DOIs
StatePublished - 2016

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Unfolded Protein Response
Homeostasis
Acinar Cells
Maintenance
Phenotype
Protein Unfolding
Chromatin Immunoprecipitation
Metaplasia
Transcriptome
Pancreatitis
Genes
Cell Differentiation
Stomach
Adenocarcinoma
Transcription Factors
Pathology
Gene Expression
Health
Wounds and Injuries
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Hoang, C. Q., Hale, M. A., Azevedo-Pouly, A. C., Elsässer, H. P., Deering, T. G., Willet, S. G., ... MacDonald, R. J. (2016). Transcriptional maintenance of pancreatic acinar identity, differentiation, and homeostasis by PTF1A. Molecular and Cellular Biology, 36(24), 3033-3047. https://doi.org/10.1128/MCB.00358-16

Transcriptional maintenance of pancreatic acinar identity, differentiation, and homeostasis by PTF1A. / Hoang, Chinh Q.; Hale, Michael A.; Azevedo-Pouly, Ana C.; Elsässer, Hans P.; Deering, Tye G.; Willet, Spencer G.; Pan, Fong C.; Magnuson, Mark A.; Wright, Christopher V E; Swift, Galvin H.; MacDonald, Raymond J.

In: Molecular and Cellular Biology, Vol. 36, No. 24, 2016, p. 3033-3047.

Research output: Contribution to journalArticle

Hoang, CQ, Hale, MA, Azevedo-Pouly, AC, Elsässer, HP, Deering, TG, Willet, SG, Pan, FC, Magnuson, MA, Wright, CVE, Swift, GH & MacDonald, RJ 2016, 'Transcriptional maintenance of pancreatic acinar identity, differentiation, and homeostasis by PTF1A', Molecular and Cellular Biology, vol. 36, no. 24, pp. 3033-3047. https://doi.org/10.1128/MCB.00358-16
Hoang, Chinh Q. ; Hale, Michael A. ; Azevedo-Pouly, Ana C. ; Elsässer, Hans P. ; Deering, Tye G. ; Willet, Spencer G. ; Pan, Fong C. ; Magnuson, Mark A. ; Wright, Christopher V E ; Swift, Galvin H. ; MacDonald, Raymond J. / Transcriptional maintenance of pancreatic acinar identity, differentiation, and homeostasis by PTF1A. In: Molecular and Cellular Biology. 2016 ; Vol. 36, No. 24. pp. 3033-3047.
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