This repo contains the code used to make the analysis and figures for the paper "Hepatocyte dedifferentiation in 2D culture reveals extensive transcriptomic and proteomic rewiring" published in Hepatology Communications October 2025. The paper can be found here
The project investigates the dedifferentiation of primary mouse hepatocytes in 2D culturing using bulk RNA sequencing, single nucleus RNAseq, and proteomics. The project found that 24 hours of culturing causes major changes to the hepatocyte proteome- and transcriptome, and also highlighted key difference between protein abundance and RNA expression for proteins/genes of mitochondrial origin.
Data can be explored in our companion app Hepamorphosis found here A separate github page has been made with the hepamorphosis code
Due to the size of Single nucleus RNAseq objects, we cannot upload the R objects used to generate the figures. Data is available through GEO for bulk RNAseq, for single-nucleus RNAseq and PRIDE for proteomics. We encourage anyone who wishes to replicate our analysis to contact us. We have attempted to share as much code as possible.
The project was initiated with the intention of using the Targets framework. However, during the process we discovered that Targets does not play well with Seurat objects, and results in slow processing and very large Targets objects. Hence, Targets is only utilized for bulk RNAseq and proteomics analysis, and the scripts are essentially split in two; a Targets part (bulk RNA + proteomics) and a non-targets part (single-nucleus).
The Targets pipeline can be found in the targets file. Functions can be found in the R folder for bulk RNA and proteomics
Figures for the Targets Work can be found here
Functions for single nucleus RNAseq can be found here
The analysis and figure generation can be found here
For more information on this project please contact Morten Dall.