Evidence for a terminal differentiation process in the rat liver

Samuel H. Sigal, Sanjeev Gupta, D. F. Gebhard, P. Holst, David S. Neufeld, L. M. Reid

Research output: Contribution to journalArticle

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Abstract

In rapidly renewing epithelia, such as skin and gut, as well as hemopoietic cells and stromal fibroblasts, the process of progenitor cell maturation, terminal differentiation and senescence from cells of a fetal phenotype is strikingly similar. To examine hepatocellular maturation, we studied embryonic, suckling and young adult rat liver cells with multiparametric fluorescence activated cell sorting (FAGS), after exclusion of hemopoietic, endothelial, Kupffer, and nonviable cells. With maturation, cell granularity and autofluorescence exponentially increased from fetal liver to suckling and adult liver as the proportion of S phase cells progressively declined from 33.8%±1.3% to 4.9%±2.8% and 1.1%±0.6% (P<0.05), respectively. In liver from fetal and suckling rats, all hepatocytes were mononuclear and contained diploid DNA whereas 21.2%±5.9% hepatocytes in adult liver were binucleated. Analysis of nuclear DNA content in adult hepatocytes demonstrated that 53.3%±3.9% of the nuclei were diploid, 43.6%±3.5% tetraploid and 0.5±0.6% octaploid. However, in the adult liver, small, mononuclear cells were also present with granularity and autofluorescence comparable to fetal hepatoblasts, as well as glucose-6-phosphatase activity, diploid DNA in 89.0%±2.1% of the nuclei, and with increased granularity in culture. Since general features of terminal cellular differentiation and senescence include cessation of mitotic activity, polyploidy and accumulation of autofluorescent secondary lysosomes, our data suggest that liver cells too undergo a process of terminal differentiation.

Original languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalDifferentiation
Volume59
Issue number1
DOIs
StatePublished - 1995

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Liver
Diploidy
Hepatocytes
Cell Aging
DNA
Glucose-6-Phosphatase
Polyploidy
Kupffer Cells
Tetraploidy
Stromal Cells
Lysosomes
S Phase
Cell Differentiation
Young Adult
Flow Cytometry
Stem Cells
Epithelium
Fibroblasts
Phenotype
Skin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Evidence for a terminal differentiation process in the rat liver. / Sigal, Samuel H.; Gupta, Sanjeev; Gebhard, D. F.; Holst, P.; Neufeld, David S.; Reid, L. M.

In: Differentiation, Vol. 59, No. 1, 1995, p. 35-42.

Research output: Contribution to journalArticle

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