Mario Brosch

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 ...

DEEP-HCC - Detailed Analysis of the Spatial Organization of the Development of Hepatocellular Carcinoma

This generic project is intended to be a forum for all LiSyM partner and external stakeholders interested in participating in the BMBF initiative LiSyM-Krebs.

This comprises the whole LiSyM network

One of the tasks of the healthy liver is to store fat. Yet, at some stage, too much fat makes the liver sick. One critical time point occurs when a healthy fatty liver becomes inflamed and progresses to steatohepatitis, or NASH. LiSyM-Pillar I will identify what events lead to this transition. Does it occur in all parts of the liver? Which molecules indicate that it is taking place? Can the degeneration be stopped or undone - and if so, how?

To investigate the underlying molecular principles of metabolic and morphogenic zonation of the human liver lobule, we generated an integrated epigenetic map across three zones (pericentral, intermediate and periportal) by methylation and transcriptomic analysis of hepatocytes captured by laser micro-dissection. We observe a deep link between epigenetic zonation of human liver and a zonated expression of metabolic and morphogenic pathways: Key transcriptionally zonated enzymes in xenobiotic and ...

The study comprises 19 human liver biopsy donors divided into the groups normal control (NC = 7012, 7173, 7194, 7279), healthy obese (HO = 6758, 6922, 7213, 7230, 7252), bland steatosis (STEA = 6967, 7137, 7172, 7181, 7251) and early NASH (EARLY = 6610, 7041, 7157, 7188, 7344).

Hepatocytes captured by laser microdissection were obtained from three hepatic zones (pericentral, intermediate and periportal) and subjected to reduced representation bisulfite sequencing and RNA-seq resulting in 114 ...

Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: pericentral (CV)

DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; hepatic zone: pericentral (CV)

Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: intermediate (IZ)

Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: periportal (PP)

DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; hepatic zone: intermediate (IZ)

DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; periportal (PP)

Experimental assay Human-NAFLD/HO , 4 biopsies from healthy obese patients. Samples for the HO category were obtained in patients undergoing bariatric surgery with a BMI > 30 and subgroups defined by liver histology as follows: HO samples showed a normal liver histology such as the NC samples.

-h692a -h6758 -h6922 -h7230

All file here

Files can be opened and visualised with http://motiontracking.mpi-cbg.de/get/ software

Experimental assay Human-NAFLD/NC 6 biopsies from normal control patients. : NC samples showed steatosis ≤5%, no inflammation, no ballooning and no fibrosis and were obtained during liver resections or biopsy in non-hepatobiliary malignancy in patients with a BMI<30kg/m2. Livers were either free of metastases or a distance of at least 2 cm to the next metastasis observed.

Image data for this assay available via link to file folder containing ...

Human RNA-Seq data set GSM2819712 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819698 stored in NCBI (GEO)

liver tissue sample : 6922_IZ_RNA

Human RNA-Seq data set GSM2819714 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819713 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819711 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819710 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819709 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819695 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819694 stored in NCBI (GEO)

Human RNA-Seq data set GSM2819693 stored in NCBI (GEO)

SOP : liver tissue microdissection for RNA sequencing

Talk at the Jamboree 2021 about epigenomic map of human liver zonation and loss of zonation in end-stage liver disease

Human microdissected liver tissue sample