Liver App

Kaessmann Lab More apps

This app accompanies the paper The origin and molecular evolution of the mammalian liver cell architecture.

It enables the interactive exploration of the snRNA-seq, snATAC-seq and spatial sequencing data of the livers of the species described in the paper.

Here you can visualize the snRNA-seq annotation and gene expression data. Select a cell label and a gene of interest (start typing the name to get autocomplete hints for available gene names). You can select the species of the gene identifiers, however, the orthologs are always retrieved from human. Then, select one or more species to view. Finally, press the 'Show plots' button to generate or update the plots.

Here you can see the zonation scores of genes in hepatocytes across species. Select a gene of interest (start typing the name to get autocomplete hints for available gene names). You can select the species of the gene identifiers, however, the orthologs are always retrieved from human. Then, select one or more species to view. Finally, press the 'Show plots' button to generate or update the plots.

Here you can visualize the snATAC-seq annotation and gene score data. Select a cell label and a gene of interest (start typing the name to get autocomplete hints for available gene names). You can select the species of the gene identifiers, however, the orthologs are always retrieved from human. Then, select one or more species to view. Finally, press the 'Show plots' button to generate or update the plots.

Here, you can visualize the annotation and gene expression in the spatial transcriptomics data (10X Visium). Select a gene of interest (start typing the name to get autocomplete hints for available gene names) and one or more species to view. Finally, press the 'Show plots' button to generate or update the plots.

Here, you can visualize the annotation and gene expression in the spatial transcriptomics data (10X Visium HD). Select a gene of interest (start typing the name to get autocomplete hints for available gene names) and one or more datasets to view. Finally, press the 'Show plots' button to generate or update the plots.

In the spatial annotation plots, only the portal and central hepatocyte bins are displayed. Bins that were filtered out in quality control or contained mixed signatures are not plotted. In the spatial gene expression plots, expression levels across the whole datasets are displayed.

This tab also shows scatterplots of the expression of genes in hepatocytes across the zonation axis for each species. The mouse scatterplot contains the combined results of the male and female datasets.

Information & Data

Reference

Origins and molecular evolution of the mammalian liver cell architecture.
Xuefei Yuan, Leticia Rodríguez-Montes, Bastienne Zaremba, Nils Trost, Céline Schneider, Julia Schmidt, Bianka Berki, Evgeny Leushkin, David Ibberson, Birgit Nickel, Miklós Palkovits, Richard W. Truman, Greg Barsh, John Lees, Amir Fallahshahroudi, Frank Grützner, Athanasia Tzika, Michel Milinkovitch, Svante Pääbo, Margarida Cardoso-Moreira, Henrik Kaessmann

Abstract

The liver is a central organ with essential roles in processes such as nutritional metabolism, detoxification, and immune defense. It has been instrumental in the adaptation of mammalian species to diverse environments, as reflected by its rapid molecular evolution. However, the origins and evolutionary dynamics of liver cell types and their structural organization remain largely unexplored. Here we report evolutionary analyses of transcriptome and chromatin accessibility data for liver cells from 17 species, spanning all major feeding strategies (herbivory, omnivory, carnivory, insectivory), great apes (including humans), placental clades (Afrotheria, Xenarthra, Laurasiatheria, Euarchontoglires), major mammalian lineages (placentals, marsupials, monotremes), and a bird as outgroup. Integrated with spatial transcriptomics, our data reveal that liver zonation—the compartmentalization of hepatocyte functions along the lobule, the liver’s fundamental anatomical and functional unit—is conserved across mammals but absent in other vertebrates. We find that zonation originated in the mammalian ancestor, driven by the emergence of WNT and R-spondin signaling from central vein endothelial cells, which activate central hepatocyte gene expression via the transcription factor TCF7L2. Despite this conserved architecture and signaling, genes with zonated expression exhibit rapid evolutionary turnover. Consistently, hepatocytes evolve fast, likely due to reduced pleiotropic constraints, enabling adaptive changes under positive selection. Alongside immune cells, hepatocytes are therefore key drivers of the liver's rapid evolution and functional innovations. In great apes, we identify human-specific shifts in zonation and cell-type-specific expression linked to recent cis-regulatory changes, particularly in genes involved in lipid metabolism, likely contributing to human-specific metabolic traits. Our study uncovers the origins of a mammal-specific liver cell architecture, within which reduced constraints and positive selection facilitated molecular changes underlying ecological adaptations.

Data

Genome-wide chromatin accessibility profiles for the 13 species are available on UCSC genome browser:

snRNA-seq Seurat objects: