Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Evidence For A Terminal Differentiation Process In The Rat Liver.

S. Sigal, S. Gupta, D. Gebhard, P. Holst, D. Neufeld, L. Reid
Published 1995 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
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 cellularity 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.
This paper references
10.1021/BI00350A005
Basement membrane complexes with biological activity.
H. Kleinman (1986)
10.1016/0014-4827(64)90165-X
CHANGES IN THE REPLICATION TIMES AND PATTERNS OF THE LIVER CELL DURING THE LIFE OF THE RAT.
J. Post (1964)
Cell lineages and oval cell progenitors in rat liver development.
N. Shiojiri (1991)
10.1016/S0022-5320(72)90080-9
Electron microscopical studies on rat brain neurons. Localization of acid phosphatase and mode of formation of lipofuscin bodies.
U. Brunk (1972)
10.1002/CYTO.990030503
A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis.
L. Vindeløv (1983)
10.1177/17.8.517
HISTOCHEMICAL AND ULTRASTRUCTURAL DEMONSTRATION OF γ-GLUTAMYL TRANSPEPTIDASE ACTIVITY
A. Rutenburg (1969)
Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine.
J. Lemire (1991)
10.1016/0014-4827(71)90685-9
Polyploid series of mammalian cells.
Michael H. Harris (1971)
10.1093/CARCIN/5.10.1267
Emergence of a population of small, diploid hepatocytes during hepatocarcinogenesis.
P. Schwarze (1984)
10.1093/GERONJ/23.2.145
Lipofuscin pigment accumulation and distribution in five rat organs as a function of age.
W. Reichel (1968)
10.1002/HEP.1840160224
Small cell colonies appear in the primary culture of adult rat hepatocytes in the presence of nicotinamide and epidermal growth factor
T. Mitaka (1992)
10.1016/0014-4827(82)90189-6
Isolation of autofluorescent "aged" human fibroblasts by flow sorting. Morphology, enzyme activity and proliferative capacity.
J. F. Jongkind (1982)
10.1111/J.1600-0676.1988.TB00972.X
The streaming liver. II. Hepatocyte life history.
N. Arber (1988)
10.1111/j.1749-6632.1980.tb29521.x
CELL TYPES IN LONG‐TERM PROPAGABLE CULTURES OF RAT LIVER *
J. Grisham (1980)
10.1159/000163565
An antigenic portrait of the liver during carcinogenesis.
D. Hixson (1990)
10.1002/JCP.1041390328
Proliferation of fetal rat hepatocytes in response to growth factors and hormones in primary culture
B. Hoffmann (1989)
10.1042/BJ2470023
Fluorescence-activated sorting of rat hepatocytes based on their mixed function oxidase activities towards diethoxyfluorescein.
I. H. White (1987)
10.1016/0014-4827(73)90394-7
Cellular senescence and DNA synthesis. Thymidine incorporation as a measure of population age in human diploid cells.
V. Cristofalo (1973)
Evidence for the stem cell origin of hepatocellular carcinoma and cholangiocarcinoma.
S. Sell (1989)
10.1016/0531-5565(80)90083-2
A new human diploid cell strain, TIG-1, for the research on cellular aging
M. Ohashi (1980)
10.1002/PATH.1700760213
Role of cholangioles in restoration of the liver of the mouse after dietary injury
Wilson Jw (1958)
Extracellular matrix : chemistry, biology, and pathobiology with emphasis on the liver
M. Zern (1993)
10.1016/S0074-7696(08)60100-X
Cell polyploidy: its relation to tissue growth and function.
W. Brodsky (1977)
Isolation of oval cells by centrifugal elutriation and comparison with other cell types purified from normal and preneoplastic livers.
P. Yaswen (1984)
10.1016/0012-1606(70)90138-7
Changes in the distribution of thymidine-3H labeled cells in the growing liver acinus of neonatal rats.
A. V. Lebouton (1970)
10.1002/HEP.1840160130
Lipopolysaccharide treatment of rats alters antigen expression and oxidative metabolism in hepatic macrophages and endothelial cells
Thomas W. Mc Closkey (1992)
Biliary epithelial and hepatocytic cell lineage relationships in embryonic rat liver as determined by the differential expression of cytokeratins, alpha-fetoprotein, albumin, and cell surface-exposed components.
L. Germain (1988)
10.1083/JCB.49.2.264
DIFFERENTIATION OF ENDOPLASMIC RETICULUM IN HEPATOCYTES : I. Glucose-6-Phosphatase Distribution In Situ.
A. Leskes (1971)
Demonstration of glucose-6-phosphatase and peroxisomal catalase activity by ultrastructural cytochemistry in oval cells from livers of carcinogen-treated rats.
F. Plénat (1988)
10.1016/0309-1651(80)90077-6
Endopolyploidy in vertebrate liver: an evolutionary perspective.
K. Brasch (1980)
10.1002/JCP.1041220116
Differential responsiveness of cultured suckling and adult rat hepatocytes to growth‐promoting factors: Entry into s phase and mitosis
H. Baribault (1985)
10.1093/CARCIN/13.2.271
Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethionine-supplemented diet.
H. Hacker (1992)
10.1016/0006-291X(87)90964-8
Analysis by flow cytometry of rat hepatocytes from different acinar zones.
J. L. Vargas (1987)
10.1152/AJPGI.1992.263.2.G139
The liver as a stem cell and lineage system.
S. Sigal (1992)
10.1016/S0022-5320(72)80005-4
Ultrastructural changes accompanying the aging of human diploid cells in culture.
J. Lipetz (1972)
10.1002/HEP.1840190427
Characterization and enrichment of fetal rat hepatoblasts by immunoadsorption (“panning”) and fluorescence‐activated cell sorting
S. Sigal (1994)
10.1093/JNCI/46.6.1261
Chromosome patterns in rat hepatocytes during N-2-fluorenylacetamide carcinogenesis.
F. Becker (1971)



This paper is referenced by
10.1152/ajpgi.1999.276.5.G1260
Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events.
S. Sigal (1999)
10.1007/978-1-62703-098-4_10
Regenerative Therapies for Liver Diseases
A. Sharma (2013)
10.1007/978-1-59259-411-5_36
Transplantation of Hepatic Stem Cells and Potential Applications for Cell Therapy
S. Gupta (2004)
10.1006/EXCR.1998.4088
Transforming Growth Factor-β (TGF-β) and EGF Promote Cord-like Structures That Indicate Terminal Differentiation of Fetal Hepatocytes in Primary Culture
A. Sánchez (1998)
10.25560/4727
Role of FXR in the adaptive response to bile acids during pregnancy
A. Milona (2009)
10.1074/JBC.M300982200
Liver Cell Polyploidization: A Pivotal Role for Binuclear Hepatocytes*
Jacques-Emmanuel Guidotti (2003)
10.1016/0169-409X(95)00061-B
Phenotype and regulation of hepatic progenitor cells versus mature liver cells
Shlomo Brill (1995)
10.1074/JBC.M210391200
Citron Kinase Is a Cell Cycle-dependent, Nuclear Protein Required for G2/M Transition of Hepatocytes*
H. Liu (2003)
10.1177/096368979800700304
Response of Cultured Fetal and Adult Rat Hepatocytes to Growth Factors and Cyclosporine
H Lilja (1998)
10.18632/AGING.100074
A structural basis for cellular senescence
A. Aranda-Anzaldo (2009)
10.1016/j.mad.2005.01.011
Natural ageing in the rat liver correlates with progressive stabilisation of DNA–nuclear matrix interactions and withdrawal of genes from the nuclear substructure
Apolinar Maya-Mendoza (2005)
10.1074/jbc.M308406200
Vascular Smooth Muscle Polyploidization as a Biomarker for Aging and Its Impact on Differential Gene Expression*
M. Jones (2004)
10.1002/jcp.10057
Functional analysis of mouse hepatocytes differing in DNA content: Volume, receptor expression, and effect of IFNγ
N. Martin (2002)
10.1046/j.1524-475x.2001.00467.x
The role of progenitor cells in repair of liver injury and in liver transplantation
S. Sell (2001)
10.1016/B978-012436636-7/50126-9
Liver Cell Culture and Lineage Biology
J. M. Macdonald (2002)
10.1111/J.1530-0277.2001.TB02190.X
Summary report of a symposium: genes and gene delivery for diseases of alcoholism.
F. Crews (2001)
10.4161/cib.18761
The post-mitotic state in neurons correlates with a stable nuclear higher-order structure
A. Aranda-Anzaldo (2012)
10.1136/gut.2004.043893
Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis
H. Toyoda (2005)
10.1006/SCBI.2000.0317
Hepatic polyploidy and liver growth control.
S. Gupta (2000)
10.1074/JBC.M108253200
Cloning and Characterization of Liver-specific Isoform of Chk1 Gene from Rat*
Y. Shann (2001)
10.1007/978-3-642-72149-6_5
Mechanisms of cell cycle blocks at the G2/M transition and their role in differentiation and development.
M. Mowat (1998)
10.1136/gut.2005.064477
Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo
G. Nowak (2005)
10.1016/S0091-679X(08)00008-3
Hepatic stem cells and hepatoblasts: identification, isolation, and ex vivo maintenance.
Eliane L Wauthier (2008)
10.1016/B978-012369410-2.50022-X
20 – Hepatic Stem Cells: Lineage Biology and Pluripotency
Nancy Cheng (2008)
10.1002/HEP.510310113
Heterogeneity of growth potential of adult rat hepatocytes in vitro
C. Tateno (2000)
Università degli Studi di Milano Scuola di Dottorato in Medicina Molecolare
S. Bosari (2012)
Hyaluronan hydrogels, 3-dimensional scaffolds for ex vivo maintenance of human hepatic stem cells and hepatoblasts
W. Turner (2007)
10.1016/B978-0-12-398358-9.00045-8
Liver Stem Cells
R. Manohar (2014)
Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes.
H. Malhi (2002)
10.1007/s10522-010-9285-4
Aged and post-mitotic cells share a very stable higher-order structure in the cell nucleus in vivo
Janeth Alva-Medina (2010)
10.1152/ajpgi.1999.276.5.G1260
Partial hepatectomy-induced polyploidy attenuates hepatocyte replication and activates cell aging events.
S. Sigal (1999)
10.1038/nrg2937
Methods for making induced pluripotent stem cells: reprogramming à la carte
Federico González (2011)
See more
Semantic Scholar Logo Some data provided by SemanticScholar