Characterization of liver macrophages (LMs) in human liver tissue sections

LMs were characterized in human liver tissue sections using immunohistochemistry and bioinformatic image analysis. Isolated cells were characterized in suspension using FACS analyses and in culture using

Submitter: René Hänsel

Assay type: Image Collection

Technology type: Imaging

Investigation: Role of liver macrophages in different liver pa...

Study: In vivo and in vitro characterization of primar...

Hepatocellular Carcinoma

The model studies the influence of hepatocyte–sinusoid alignment (HSA), i.e. the orientation of the division plane such that daughter hepatocytes align with nearby sinusoids, on the shape of tumor nodules in liver lobules. It employs the structure of the model ‘Liver Regeneration from CCl4’ (https://seek.lisym.org/models/19).

Originally, Höhme et al. (https://doi.org/10.1007/s11538-017-0375-1) employed a center-based model. Here, the model is encoded in the standardized language MorpheusML. ...

Creators: Diego Jahn, Michael Kücken, Lutz Brusch

Submitter: Diego Jahn

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Liver Regeneration from CCl4

In the experimental paradigm of CCl4 intoxication of mice, hepatocytes around the central vein (located in the center of an idealized hexagonal liver lobule) are dying and are subsequently replaced by new hepatocytes, largely through activation of proliferation in the remaining hepatocytes.

Alignment of daughter hepatocytes along the orientation of the closest sinusoid, a process which is named hepatocyte-sinusoid alignment (HSA), was proposed by Höhme et al. (https://doi.org/10.1073/pnas.0909374107) ...

Creators: Diego Jahn, Michael Kücken, Lutz Brusch

Submitter: Diego Jahn

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IFNalpha-induced signaling in Huh7.5 cells

ODE model describes dynamics of IFNalpha-induced signaling in Huh7.5 cells for a time scale up to 32 hours after stimulation with IFNalpha. The model consists of an IFN receptor model, formation/degradation and cytoplasmic/nuclear shuttling of STAT1-homodimers, STAT1-STAT2-heterodimers and STAT1-STAT2-IRF9 (ISGF3) complexes. On top, formation of feedback proteins STAT1, STAT2, IRF9, USP18, SOCS1, SOCS3 and IRF2 and corresponding influences on IFNalpha signaling dynamics was incorporated. The model ...

Creators: Jens Timmer, Ursula Klingmüller, Daniel Seehofer, Marcus Rosenblatt, Krishna Kumar Tiwari, Frédérique Kok

Submitter: Olga Krebs

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SOP: Analysis of Mouse Liver Glycogen Content

Liver is the major site for glycogen storage. Glycogen content can be significantly altered upon disruption of glucose homeostasis in metabolic syndromes, such as diabetes.

Glycogen content can be determined by an acid-hydrolysis method . Basically, glucose, the hydrolysis product of glycogen, is converted into glucose-6- phosphate (G-6-P) by hexokinase in the presence of ATP.

With the supply of NADP, G-6-P is further converted into 6-phosphogluconic acid by G-6-P dehydrogenase (G-6-PDH), while ...

Creator: Olga Krebs

Submitter: Olga Krebs

FitMultiCell: simulating and parameterizing computational models of multi-scale and multi-cellular processes.

Abstract (Expand)

MOTIVATION: Biological tissues are dynamic and highly organized. Multi-scale models are helpful tools to analyse and understand the processes determining tissue dynamics. These models usually depend … on parameters that need to be inferred from experimental data to achieve a quantitative understanding, to predict the response to perturbations, and to evaluate competing hypotheses. However, even advanced inference approaches such as approximate Bayesian computation (ABC) are difficult to apply due to the computational complexity of the simulation of multi-scale models. Thus, there is a need for a scalable pipeline for modeling, simulating, and parameterizing multi-scale models of multi-cellular processes. RESULTS: Here, we present FitMultiCell, a computationally efficient and user-friendly open-source pipeline that can handle the full workflow of modeling, simulating, and parameterizing for multi-scale models of multi-cellular processes. The pipeline is modular and integrates the modeling and simulation tool Morpheus and the statistical inference tool pyABC. The easy integration of high-performance infrastructure allows to scale to computationally expensive problems. The introduction of a novel standard for the formulation of parameter inference problems for multi-scale models additionally ensures reproducibility and reusability. By applying the pipeline to multiple biological problems, we demonstrate its broad applicability, which will benefit in particular image-based systems biology. AVAILABILITY AND IMPLEMENTATION: FitMultiCell is available open-source at https://gitlab.com/fitmulticell/fit.

Authors: E. Alamoudi, Y. Schalte, R. Muller, J. Starruss, N. Bundgaard, F. Graw, L. Brusch, J. Hasenauer

Date Published: 1st Nov 2023

Publication Type: Journal

Apical bulkheads accumulate as adaptive response to impaired bile flow in liver disease.

Abstract (Expand)

Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic … development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.

Authors: C. Mayer, S. Nehring, M. Kucken, U. Repnik, S. Seifert, A. Sljukic, J. Delpierre, H. Morales-Navarrete, S. Hinz, M. Brosch, B. Chung, T. Karlsen, M. Huch, Y. Kalaidzidis, L. Brusch, J. Hampe, C. Schafmayer, M. Zerial

Date Published: 31st Jul 2023

Publication Type: Journal

Diploid hepatocytes drive physiological liver renewal in adult humans

Abstract (Expand)

Physiological liver cell replacement is central to maintaining the organ’s high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (14C) … birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age <3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics.

Authors: Paula Heinke, Fabian Rost, Julian Rode, Palina Trus, Irina Simonova, Enikő Lázár, Joshua Feddema, Thilo Welsch, Kanar Alkass, Mehran Salehpour, Andrea Zimmermann, Daniel Seehofer, Göran Possnert, Georg Damm, Henrik Druid, Lutz Brusch, Olaf Bergmann

Date Published: 1st Jun 2022

Publication Type: Journal

Human microdissected liver tissue sample (GEO)

Human microdissected liver tissue sample

Published sample ID (String) *, Lab sample ID (String) *, Tissue (Controlled Vocabulary - Liver cell types) *, Organism (NCBI ID) , Sample web link (Web link) , Link to SOP used (Web link) , hepatic zone (Controlled Vocabulary - Hepatic zones in human hepatocytes) , Sample creation date (Date) , Molecule type (String)

liver, hepatocite, Human

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