Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state

Sanjeev Gupta, Pankaj Rajvanshi, Rana P. Sokhi, Shilpa Vaidya, Adil N. Irani, Giridhar R. Gorla

Research output: Contribution to journalArticle

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Abstract

Mechanisms directing position-specific liver gene regulation are incompletely understood. To establish whether this aspect of hepatic gene expression is an inveterate phenomenon, we used transplanted hepatocytes as reporters in dipeptidyl peptidase IV-deficient F344 rats. After integration in liver parenchyma, the position of transplanted cells was shifted from periportal to perivenous areas by targeted hepatic ablations with carbon tetrachloride. In controls, transplanted cells showed greater glucose-6- phosphatase and lesser glycogen content in periportal areas. This pattern was reversed when transplanted cells shifted from periportal to perivenous areas. Transplanted hepatocytes in perivenous areas exhibited inducible cytochrome P450 activity, which was deficient in periportal hepatocytes. Moreover, cytochrome P450 activity was rapidly extinguished in activated hepatocytes when these cells were transplanted into the nonpermissive liver of suckling rat pups. In cells isolated from the normal F344 rat liver, cytochrome P450 inducibility was originally greater in perivenous hepatocytes; however, periportal cells rapidly acquired this facility in culture conditions. These findings indicate that the liver microenvironment exerts supremacy over prior differentiation state of cells in directing position-specific gene expression. Therefore, persistence of specialized hepatocellular function will require interactions with regulatory signals and substrate availability, which bears upon further analysis of liver gene regulation, including in progenitor and/or stem cells.

Original languageEnglish (US)
Pages (from-to)2157-2165
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number4
DOIs
StatePublished - Jan 22 1999

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Gene expression
Liver
Cell Differentiation
Gene Expression
Hepatocytes
Cytochrome P-450 Enzyme System
Rats
Inbred F344 Rats
Dipeptidyl Peptidase 4
Glucose-6-Phosphatase
Stem Cells
Carbon Tetrachloride
Ablation
Stem cells
Glycogen
Availability
Genes
Substrates

ASJC Scopus subject areas

  • Biochemistry

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Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state. / Gupta, Sanjeev; Rajvanshi, Pankaj; Sokhi, Rana P.; Vaidya, Shilpa; Irani, Adil N.; Gorla, Giridhar R.

In: Journal of Biological Chemistry, Vol. 274, No. 4, 22.01.1999, p. 2157-2165.

Research output: Contribution to journalArticle

Gupta, Sanjeev ; Rajvanshi, Pankaj ; Sokhi, Rana P. ; Vaidya, Shilpa ; Irani, Adil N. ; Gorla, Giridhar R. / Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 4. pp. 2157-2165.
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