Differentiation-specific regulation of transgene expression in a diploid epithelial cell line derived from the normal F344 rat liver

Michael Ott, Pankaj Rajvanshi, Rana P. Sokhi, Gianfranco Alpini, Emma Aragona, Mariana Dabeva, David A. Shafritz, Sanjeev Gupta

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

To establish the differentiation potential of progenitor cells, non- parenchymal epithelial cells from the F344 rat liver (FNRL cells) were studied. These cells reacted with the OV-6 antibody marker of oval cells, but were negative for hepatocyte markers (albumin, transferrin, glycogen, glucose-6-phosphatase, H4 antigen), biliary markers (gamma glutamyl transpeptidase, cytokeratin-19), and α-fetoprotein, although exposure to sodium butyrate induced nascent albumin and α-fetoprotein mRNA transcription. When stably transduced, FNRL cells expressed a retrovital promotor-driven lacZ reporter in vitro, similar to transgene expression in hepatocyte-derived HepG2 cells. However, lacZ expression in FNRL cells was rapidly extinguished in intact animals, whereas the reporter remained active in HepG2 cells. Transplanted FNRL cells showed copious glucose-6-phosphatase expression; however, the cell differentiation programme remained incomplete, despite two-thirds partial hepatectomy, D-galactosamine treatment or bile duct ligation. Interestingly, lacZ expression resumed in cultures of FNRL cells explanted from recipients. Moreover, lacZ expression was down-regulated by γ-interferon in FNRL cells, without affecting lacZ activity in HepG2 cells. The data indicate that although subpopulations of oval cells may not fully differentiate into mature hepatocytes, these cells might serve critical functions, such as glucose utilization, and help survival after liver injury. Also, introduced genes may be regulated in progenitor cells at multiple levels, including by interactions between regulatory sequences, differentiation-specific cellular factors, and extracellular signals; in vivo studies are thus especially important for analyzing gene regulation in progenitor cells.

Original languageEnglish (US)
Pages (from-to)365-373
Number of pages9
JournalJournal of Pathology
Volume187
Issue number3
DOIs
StatePublished - 1999

Fingerprint

Inbred F344 Rats
Diploidy
Transgenes
Epithelial Cells
Cell Line
Liver
Hep G2 Cells
Fetal Proteins
Hepatocytes
Glucose-6-Phosphatase
Stem Cells
Albumins
Keratin-19
Galactosamine
Butyric Acid
gamma-Glutamyltransferase
Differentiation Antigens
Hepatectomy
Transferrin
Bile Ducts

Keywords

  • Cell line
  • Differentiation
  • Gene expression
  • Liver
  • Regeneration

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Differentiation-specific regulation of transgene expression in a diploid epithelial cell line derived from the normal F344 rat liver. / Ott, Michael; Rajvanshi, Pankaj; Sokhi, Rana P.; Alpini, Gianfranco; Aragona, Emma; Dabeva, Mariana; Shafritz, David A.; Gupta, Sanjeev.

In: Journal of Pathology, Vol. 187, No. 3, 1999, p. 365-373.

Research output: Contribution to journalArticle

Ott, Michael ; Rajvanshi, Pankaj ; Sokhi, Rana P. ; Alpini, Gianfranco ; Aragona, Emma ; Dabeva, Mariana ; Shafritz, David A. ; Gupta, Sanjeev. / Differentiation-specific regulation of transgene expression in a diploid epithelial cell line derived from the normal F344 rat liver. In: Journal of Pathology. 1999 ; Vol. 187, No. 3. pp. 365-373.
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AU - Aragona, Emma

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AU - Shafritz, David A.

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