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Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control.
- Source :
-
Nature communications [Nat Commun] 2018 Oct 08; Vol. 9 (1), pp. 4150. Date of Electronic Publication: 2018 Oct 08. - Publication Year :
- 2018
-
Abstract
- A deeper epigenomic understanding of spatial organization of cells in human tissues is an important challenge. Here we report the first combined positional analysis of transcriptomes and methylomes across three micro-dissected zones (pericentral, intermediate and periportal) of human liver. We identify pronounced anti-correlated transcriptional and methylation gradients including a core of 271 genes controlling zonated metabolic and morphogen networks and observe a prominent porto-central gradient of DNA methylation at binding sites of 46 transcription factors. The gradient includes an epigenetic and transcriptional Wnt signature supporting the concept of a pericentral hepatocyte regeneration pathway under steady-state conditions. While donors with non-alcoholic fatty liver disease show consistent gene expression differences corresponding to the severity of the disease across all zones, the relative zonated gene expression and DNA methylation patterns remain unchanged. Overall our data provide a wealth of new positional insights into zonal networks controlled by epigenetic and transcriptional gradients in human liver.
- Subjects :
- Adult
Aged
Animals
DNA Methylation
Female
Gene Expression Profiling
Humans
Liver anatomy & histology
Liver growth & development
Male
Mice
Middle Aged
Non-alcoholic Fatty Liver Disease genetics
Non-alcoholic Fatty Liver Disease pathology
Epigenomics
Hepatocytes metabolism
Liver metabolism
Morphogenesis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 30297808
- Full Text :
- https://doi.org/10.1038/s41467-018-06611-5