TY - JOUR
T1 - Evidence for a terminal differentiation process in the rat liver
AU - Sigal, Samuel H.
AU - Gupta, Sanjeev
AU - Gebhard, David F.
AU - Holst, Patricia
AU - Neufeld, David
AU - Reid, Lola M.
N1 - Funding Information:
Acknowledgements. We thank Dr. Pankaj Rajvanshi for assistance with the cell culture studies and Ms Rosina Passela for secretarial assistance. This work was partly supported by an American Cancer Society Grant (BE-92C), an NIH Grant (DK44266), and a Council for Tobacco Research Grant (1897) to Dr. Reid, by the Department of Medicine, an NIH training grant (T32DK07218-17; Dr. A. Wolkoff, P.I.), and a Veronica Volk Postdoctoral Research Fellowship of the American Liver Foundation to Dr. Sigal, by NIH grants KO8 DK-01909 and RO1 DK 46952 to Dr. Gupta, and by NIH center grants to the Einstein Cancer Center (P30CA13330; Dr. M. Scharff, P.I.) and the Marion Bessin Liver Research Center (P30DK41296; Dr. D.A. Shafritz, P.I.).
PY - 1995
Y1 - 1995
N2 - 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 (FACS), 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.
AB - 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 (FACS), 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.
UR - http://www.scopus.com/inward/record.url?scp=0029166903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029166903&partnerID=8YFLogxK
U2 - 10.1046/j.1432-0436.1995.5910035.x
DO - 10.1046/j.1432-0436.1995.5910035.x
M3 - Article
C2 - 7589893
AN - SCOPUS:0029166903
SN - 0301-4681
VL - 59
SP - 35
EP - 42
JO - Differentiation
JF - Differentiation
IS - 1
ER -