Integrated epigenetic map across three hepatic zones (pericentral, intermediate and periportal) of human liver
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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 sequencing libraries. Liver samples were obtained intraoperatively in patients in whom an intraoperative liver biopsy was indicated on clinical grounds such as during scheduled liver resection, exclusion of liver malignancy during major oncologic surgery, or assessment of liver histology during bariatric surgery. NASH was defined by the NAFLD activity score (NAS) PMID: 15915461. Patients with evidence of viral hepatitis, hemochromatosis, or alcohol consumption greater than 20 g/day for women and 30 g/day for men were excluded.
All patients provided written informed consent. The study protocol was approved by the institutional review board (Ethikkommission der Medizinischen Fakultät der Universität Kiel, D425/07, A111/99), before study commencement.
SEEK ID: https://seek.lisym.org/studies/45
Epigenomic analysis of micro-dissected human liver
Projects: LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI)
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Created: 13th Jul 2021 at 08:37
Last updated: 25th Oct 2022 at 08:12
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Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...
Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)
Web page: https://www.lisym.org/
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?
Programme: LiSyM: Liver Systems Medicine
Public web page: http://www.lisym.org/our-work/pillar-research/zones-of-the-liver
Start date: 1st Jan 2016
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 ...
Submitter: Mario Brosch
Studies: Integrated epigenetic map across three hepatic zones (pericentral, inte...
Assays: DNA-methylation at binding sites of uniformly expressed transcription fa..., DNA-methylation at binding sites of uniformly expressed transcription fa..., DNA-methylation at binding sites of uniformly expressed transcription fa..., Transcriptomic analysis of hepatocytes ( hepatic zone: intermediate (IZ), Transcriptomic analysis of hepatocytes ( hepatic zone: periportal (PP), Transcriptomic analysis of hepatocytes ; hepatic zone: pericentral (CV)
Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: pericentral (CV)
Submitter: Mario Brosch
Assay type: RNA-seq Profiling
Technology type: Rna-seq
Investigation: Epigenomic analysis of micro-dissected human liver
DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; hepatic zone: pericentral (CV)
Submitter: Mario Brosch
Assay type: Methylation Profiling
Technology type: Technology Type
Investigation: Epigenomic analysis of micro-dissected human liver
Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: intermediate (IZ)
Submitter: Mario Brosch
Assay type: RNA-seq Profiling
Technology type: Rna-seq
Investigation: Epigenomic analysis of micro-dissected human liver
Transcriptomic analysis of hepatocytes captured by laser micro-dissection from hepatic zone: periportal (PP)
Submitter: Mario Brosch
Assay type: RNA-seq Profiling
Technology type: Rna-seq
Investigation: Epigenomic analysis of micro-dissected human liver
DNA-methylation at binding sites of uniformly expressed transcription factors in human hepatocytes ; hepatic zone: intermediate (IZ)
Submitter: Olga Krebs
Assay type: Methylation Profiling
Technology type: Technology Type
Investigation: Epigenomic analysis of micro-dissected human liver
Human RNA-Seq data set GSM2819712 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
External LinkHuman RNA-Seq data set GSM2819698 stored in NCBI (GEO)
liver tissue sample : 6922_IZ_RNA
Creator: Mario Brosch
Submitter: Mario Brosch
Human RNA-Seq data set GSM2819714 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
Human RNA-Seq data set GSM2819713 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
Human RNA-Seq data set GSM2819711 stored in NCBI (GEO)
Creator: Mario Brosch
Submitter: Mario Brosch
SOP : liver tissue microdissection for RNA sequencing
Creator: Mario Brosch
Submitter: Mario Brosch
