Functional and structural zonal hepatocyte heterogeneity — dynamics and ontogenic development

Klinger, W; Devereux, Theodora R.; Fouts, James R.

doi:10.1016/s0232-1513(88)80100-2

Cited by 20 publications

(10 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The origin of HSCs in the adult liver, however, has remained obscure despite the initial discovery of HSCs in 1952 [6]. As HSCs constitute only 1.4% of the total liver volume and 5% of liver cell numbers [7,8], the isolation and detailed characterization of HSCs from liver has remained difficult. Recently, Geerts et al reported a method to isolate these cells from mice using density gradient centrifugation with Nycodenz [9].…”

Section: Introductionmentioning

confidence: 99%

Commitment of bone marrow cells to hepatic stellate cells in mouse

Baba

Fujii

Hirose

et al. 2004

Journal of Hepatology

153

108

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

Commitment of bone marrow cells to hepatic stellate cells in mouse

Baba

Fujii

Hirose

et al. 2004

Journal of Hepatology

153

108

View full text Add to dashboard Cite

show abstract

“…1,2 The hepatic heterogeneity is known primarily of the parenchymal cell compartment, sometimes referred to as the metabolic zonation, which is characterized by zones of similar-looking hepatocytes that are functionally distinct and structurally different. 3,4 When expressed, interestingly, the patterns of distribution are recognized alike; they manifest in the hepatic lobules basically as concentric zones, appearingly as confined to either a peripheral zone or a centrilobular zone.…”

mentioning

confidence: 99%

“…3,5,6). Reciprocally, several other enzymes are found to dominate the centrilobular zone; these include lactate dehydrogenase, glutamate dehydrogenase, glucokinase, pyruvate kinase, acetyl-Co-A carboxylase, adenosine triphosphatedependent citrate lyase, and fatty acid synthetase.…”

mentioning

confidence: 99%

“…Likewise, the P450 superfamily of isoenzymes are expressed almost exclusively in the centrilobular zone. 3,5,6 The fact that some enzymes, e.g., glutamine synthetase 7 and cytochrome P450b,e, 8 and some molecules like glucose transporter protein, 9 are demonstrated to be localized distinctly in an exceedingly limited narrow ring immediately surrounding the central vein, has promptly initiated an idea that the conventional method of expression based on peripheral-centrilobular zones, or even the traditional peripheralintermediate-centrilobular zone addressing, are no longer adequate nor sufficient.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity

1998

View full text Add to dashboard Cite

Knowledge of hepatic heterogeneity has been strikingly increased, while an accurate means for addressing intralobular positions is still lacking. We examined pig liver preparations of the gold impregnation method for vitamin A-storing lipid droplets in hepatic stellate cells. Droplet morphometry was performed under oil immersion, and the calculated volumes plotted on computerized maps. The heterogeneous results were assessed with five concentric zones and five radial regions; the latter were determined based on midseptum visualized by portal injection. Zonation and regionation thus subdivided lobules into 5-zone/5-region (5Z/5R) compartmentalization. Distribution of values exhibited a distinct zonal gradient, heightened at peripheral zones 1 and 2, decreased over intermediate zone 3 toward centrilobular zones 4 and 5; peak was always found at zone 2. Within a single zone, variations were obvious, forming a regional gradient. Values were significantly higher at periportal than midseptal regions. Digitized mapping showed that low values filled up centrilobular zones, whereas high values concentrated in periportal regions. Along the periphery, inlet venules were quantified, revealing an occurrence rate of 60% at periportal, and 5% at midseptal regions, closely compatible with the regional gradient of vitamin A-storing capacity. The interweaving between zonal and regional gradients results in a vitamin A-low territory, a compound area composed of centrilobular zones plus extensions into midseptal regions. Because the results could account for physiological and pathological events, we regard the 5Z/5R compartmentalization a model worth routine adoption for a precise description of any morphofunctionally demonstrable heterogeneity of the liver lobules. (HEPATOLOGY 1998;27:1098-1108.)Evidence has accumulated in the literature and established a unique biological nature of the liver called heterogeneity.

show abstract

“…In some organs, differences in cellular metabolism can be related to the histological architecture of the tissue; on the other hand, some organs that are rather homogeneous in their tissue structure, such as liver, may still show regional differences in metabolism (Schmidt et al, 1978). This metabolic zonation of living tissue in a normal or pathophysiological state has been subject to intensive research and is still the focus of interest of numerous scientists (reviewed by Klinger et al, 1988;Jungermann & Katz, 1989). 'Classical' techniques for the quantification of metabolic zonation are the Lowry technique (Lowry & Passonneau, 1972) and the deoxyglucose method according to Sokoloff (1978).…”

Section: Introductionmentioning

confidence: 99%

Geographical mapping of metabolites in biological tissue with quantitative bioluminescence and single photon imaging

Mueller‐Klieser

Walenta

1993

Histochem J

View full text Add to dashboard Cite

This article features a novel technique for measuring the spatial distribution of metabolites, such as ATP, glucose, and lactate, in rapidly frozen tissue. Concentration values are obtained in absolute terms and with a spatial resolution of single-cell dimension. The method is based on enzymatic reactions that link the metabolite of interest to luciferase with subsequent light emission. Using a specific array, cryosections are brought into contact with the enzymes in a well-defined, reproducible way inducing a distribution of light across the section with an intensity that is proportional to the metabolite concentration. The emitted light can be visualized through a microscope and an imaging photon counting system, and the respective image can be transferred to a computer for image analysis. Measurements in spherical cell aggregates with central necrosis demonstrate a close correlation between the distribution of ATP and of cellular viability at a microregional level. Similarly, ATP and glucose are correlated with the geometrical arrangement of more viable and more necrotic tissue regions in human melanomas xenografted in nude mice. Lactate did not show such a structure-related distribution in these tumours. Structure-related distributions of ATP, glucose, and lactate are found in cervix tumours of patients. In contrast to the heterogeneous distributions in tumours, the distribution patterns were much more homogeneous in normal tissues. Regional differences were present, but were much more gradual than in malignancies. This was illustrated for heart muscle where ATP concentrations were found that agreed with data in the literature, and that showed a decrease in periventricular areas.

show abstract

Functional and structural zonal hepatocyte heterogeneity — dynamics and ontogenic development

Cited by 20 publications

References 151 publications

Commitment of bone marrow cells to hepatic stellate cells in mouse

Commitment of bone marrow cells to hepatic stellate cells in mouse

Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity

Geographical mapping of metabolites in biological tissue with quantitative bioluminescence and single photon imaging

Contact Info

Product

Resources

About