Hepatocytes reprogram liver macrophages involving control of TGF-β activation, influencing liver regeneration and injury.

LiSyM-Krebs ist ein nationales Forschungsnetz zur Früherkennung und Prävention von Leberkrebs, das unter Verwendung des systemmedizinischen Forschungsansatzes die komplexen, dynamischen Prozesse der Krankheitsprogression analysiert, um ausgehend von den Erkenntnissen aus dem Forschungsnetz LiSyM die Entstehung von Leberkrebs besser zu verstehen, vorherzusagen und im besten Fall sogar zu verhindern. LiSyM-Krebs setzt die erfolgreichen Forschungsaktivitäten der BMBF-Vorgängerprogramme ...

Forschungsnetzwerk zur Früherkennung und Prävention- LiSyM-Krebs

Ein Netzwerk von Klinikern, Wissenschaftlern und Datenmanagern hat sich zur Aufgabe gemacht, Methoden zu entwickeln, um Patienten mit einem hohen Risiko für ein Leberkarzinom frühzeitig, in Vorstadien der Tumorentwicklung, identifizieren zu können. Gemeinsam bilden sie das „Systemmedizinische Forschungsnetzwerk zur Früherkennung und Prävention von Leberkrebs“, LiSym-Krebs, das vom Bundesministerium für Bildung und Forschung ...

C-TIP-HCC- Mechanism-based Multiscale Model to Dissect the Tipping Point from Liver Cirrhosis to Hepatocellular Carcinoma

The ultimate goal of the C-TIP-HCC is a „mechanistic multiscale model to describe dynamic changes in regenerative nodes across a tipping point (TIP) towards development in patients with cirrhosis to facilitate early monitoring and intervention“ and facilitate intervention“. To achieve this, we will conduct in-depth studies on cirrhotic regenerative nodes.

Reverse transcription PCR, flow cytometry, transcriptome, proteome, secretome, single cell analysis, and immunohistochemical methods were used to study changes in gene expression as well as the activation state of macrophages in vitro and in vivo under homeostatic conditions and after partial hepatectomy.

The liver comprises the body´s largest pool of macrophages constituting approximately 80 % of all sessile tissue macrophages of the body. After liver damage monocyte-derived macrophages are recruited into the liver and were here affected by a micro milieu which is considerably influenced by hepatocytes. Up to now the complex network that determines the differentiation and function of liver macrophages and the impact of the intercellular communication between macrophages and the other parenchymal ...

We describe a distinct macrophage population, whose presence in the liver during homoeostasis depends on recruitment signals mediated by the chemokine receptor CCR2. The identified polarization state of this population closely resembles that induced in co-culture experiments, where hepatocytes are reducing the availability of TGFb to macrophages. Accordingly, disruption of TGFb signal transduction in macrophages phenocopies the influence of hepatocytes on macrophage polarization.

Transcriptomics: the RNA expression of primary hepatocytes and BMDM (Bone Marrow–Derived acrophages) were analysed in 4 different conditions (mono- vs. co-culture, hepatocytes and macrophages) with 5 replicas each to detect the impact of hepatocytes on macrophages and vice versa.

Hepatocyte-controlled availability of activated TGFb reprograms macrophage polarization affecting liver injury and regeneration

Data deposited on the European Bioinformatics Insititute (EBI) database under accession number E-MTAB- 11727 (https://www.ebi.ac.uk/arrayexpress/experiments/ E-MTAB-11727)

Hepatocyte-controlled availability of activated TGFb reprograms macrophage polarization affecting liver injury and regeneration.

Samples in SEEK (ArrayExpress-compliant sample type https://seek.lisym.org/sample_types/21)

Hepatocytes and macrophages from mono and co-culture were harvested and prepared for mass spectrometric analysis , samples were shortly separated in a polyacrylamide gel, silver-stained, reduced, alkylated and digested with trypsin.

GEO data set

SOP: Mice hepatocytes isolation and co-cultivation with BMDM