Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD

Abstract 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 t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lorena Pantano, George Agyapong, Yang Shen, Zhu Zhuo, Francesc Fernandez-Albert, Werner Rust, Dagmar Knebel, Jon Hill, Carine M. Boustany-Kari, Julia F. Doerner, Jörg F. Rippmann, Raymond T. Chung, Shannan J. Ho Sui, Eric Simon, Kathleen E. Corey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2713bcbab254dd8beaf4a1d8cdde925
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d2713bcbab254dd8beaf4a1d8cdde925
record_format	dspace
spelling	oai:doaj.org-article:d2713bcbab254dd8beaf4a1d8cdde9252021-12-02T18:03:06ZMolecular characterization and cell type composition deconvolution of fibrosis in NAFLD10.1038/s41598-021-96966-52045-2322https://doaj.org/article/d2713bcbab254dd8beaf4a1d8cdde9252021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96966-5https://doaj.org/toc/2045-2322Abstract 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.Lorena PantanoGeorge AgyapongYang ShenZhu ZhuoFrancesc Fernandez-AlbertWerner RustDagmar KnebelJon HillCarine M. Boustany-KariJulia F. DoernerJörg F. RippmannRaymond T. ChungShannan J. Ho SuiEric SimonKathleen E. CoreyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lorena Pantano George Agyapong Yang Shen Zhu Zhuo Francesc Fernandez-Albert Werner Rust Dagmar Knebel Jon Hill Carine M. Boustany-Kari Julia F. Doerner Jörg F. Rippmann Raymond T. Chung Shannan J. Ho Sui Eric Simon Kathleen E. Corey Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD
description	Abstract 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.
format	article
author	Lorena Pantano George Agyapong Yang Shen Zhu Zhuo Francesc Fernandez-Albert Werner Rust Dagmar Knebel Jon Hill Carine M. Boustany-Kari Julia F. Doerner Jörg F. Rippmann Raymond T. Chung Shannan J. Ho Sui Eric Simon Kathleen E. Corey
author_facet	Lorena Pantano George Agyapong Yang Shen Zhu Zhuo Francesc Fernandez-Albert Werner Rust Dagmar Knebel Jon Hill Carine M. Boustany-Kari Julia F. Doerner Jörg F. Rippmann Raymond T. Chung Shannan J. Ho Sui Eric Simon Kathleen E. Corey
author_sort	Lorena Pantano
title	Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD
title_short	Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD
title_full	Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD
title_fullStr	Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD
title_full_unstemmed	Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD
title_sort	molecular characterization and cell type composition deconvolution of fibrosis in nafld
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d2713bcbab254dd8beaf4a1d8cdde925
work_keys_str_mv	AT lorenapantano molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT georgeagyapong molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT yangshen molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT zhuzhuo molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT francescfernandezalbert molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT wernerrust molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT dagmarknebel molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT jonhill molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT carinemboustanykari molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT juliafdoerner molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT jorgfrippmann molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT raymondtchung molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT shannanjhosui molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT ericsimon molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld AT kathleenecorey molecularcharacterizationandcelltypecompositiondeconvolutionoffibrosisinnafld
_version_	1718378837071364096

Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD

Ejemplares similares