Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD.

Autor: Pantano L; Harvard Chan Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, 401 Park Dr, Boston, MA, 02215, USA., Agyapong G; Liver Center, Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.; Harvard Medical School, Boston, MA, USA., Shen Y; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany., Zhuo Z; Harvard Chan Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, 401 Park Dr, Boston, MA, 02215, USA., Fernandez-Albert F; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany., Rust W; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany., Knebel D; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany., Hill J; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA., Boustany-Kari CM; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA., Doerner JF; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany., Rippmann JF; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany., Chung RT; Liver Center, Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA. Chung.Raymond@mgh.harvard.edu.; Harvard Medical School, Boston, MA, USA. Chung.Raymond@mgh.harvard.edu., Ho Sui SJ; Harvard Chan Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, 401 Park Dr, Boston, MA, 02215, USA. shosui@hsph.harvard.edu., Simon E; Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88937, Biberach Riss, Germany. eric.simon@boehringer-ingelheim.com., Corey KE; Liver Center, Division of Gastroenterology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA. kcorey@partners.org.; Harvard Medical School, Boston, MA, USA. kcorey@partners.org.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Sep 10; Vol. 11 (1), pp. 18045. Date of Electronic Publication: 2021 Sep 10.
DOI: 10.1038/s41598-021-96966-5
Abstrakt: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide. In adults with NAFLD, fibrosis can develop and progress to liver cirrhosis and liver failure. However, the underlying molecular mechanisms of fibrosis progression are not fully understood. Using total RNA-Seq, we investigated the molecular mechanisms of NAFLD and fibrosis. We sequenced liver tissue from 143 adults across the full spectrum of fibrosis stage including those with stage 4 fibrosis (cirrhosis). We identified gene expression clusters that strongly correlate with fibrosis stage including four genes that have been found consistently across previously published transcriptomic studies on NASH i.e. COL1A2, EFEMP2, FBLN5 and THBS2. Using cell type deconvolution, we estimated the loss of hepatocytes versus gain of hepatic stellate cells, macrophages and cholangiocytes with advancing fibrosis stage. Hepatocyte-specific functional analysis indicated increase of pro-apoptotic pathways and markers of bipotent hepatocyte/cholangiocyte precursors. Regression modelling was used to derive predictors of fibrosis stage. This study elucidated molecular and cell composition changes associated with increasing fibrosis stage in NAFLD and defined informative gene signatures for the disease.
(© 2021. The Author(s).)
Databáze: MEDLINE
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