@article {1616172, title = {Molecular characterization and cell type composition deconvolution of fibrosis in NAFLD}, journal = {Sci Rep}, volume = {11}, number = {1}, year = {2021}, month = {2021 Sep 10}, pages = {18045}, 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.}, issn = {2045-2322}, doi = {10.1038/s41598-021-96966-5}, author = {Pantano, Lorena and Agyapong, George and Shen, Yang and Zhuo, Zhu and Fernandez-Albert, Francesc and Rust, Werner and Knebel, Dagmar and Hill, Jon and Boustany-Kari, Carine M and Doerner, Julia F and Rippmann, J{\"o}rg F and Chung, Raymond T and Ho Sui, Shannan J and Simon, Eric and Corey, Kathleen E} }