Data availability
Liver Cell Atlas Webtool
In addition to publishing our data in different repositories such as cellxgene and NCBI (see table below for specifics of each study). All our transcriptomic data is available for further interrogation and/or download on our data portal www.livercellatlas.org. See below for examples of data available on our portal.
We are advocates of open science and keen to ensure the portal is a useful resource for the greater scientific community. As such it is important to us that the portal is as user friendly as possible. Should you have any suggestions or questions about the data please do not hesitate to reach out to us at charlotte.scott@irc.vib-ugent.be or bioit-guilliotts@irc.vib-ugent.be
Murine MAFLD/NASH
In this publication we have performed CITE-seq analysis on total CD45+ cells isolated from the livers of mice fed a standard diet (SD) or western diet (WD; fat, cholesterol and sugar) for 12, 24 and 36 weeks. In addition, we also zoomed in on the monocyte and macrophage clusters in a separate UMAP to be able to more fully interrogate the data. We also performed single cell RNA sequencing analysis of the CD45- cells isolated from the livers of the mice fed the SD or WD for 24 and 36 weeks. All datasets as presented in the publication are available here for interrogation. Genes and proteins can be searched and overall expression in the UMAPs as well as expression per cluster and in specific clusters over the course of the feeding can be displayed.
https://www.cell.com/immunity/fulltext/S1074-7613(20)30357-5
Liver Cell Atlas
The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here, we present a spatial proteogenomic atlas of the healthy human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells including a population of bile-duct lipid-associated macrophages (LAMs). We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and bile-duct LAMs. We also uncover the respective spatially-resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that bile-duct LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their crosstalk with hepatic stellate cells via the evolutionarily-conserved ALK1-BMP9/10 axis.
https://www.cell.com/cell/fulltext/S0092-8674(21)01481-1
Single Cell RNA-Seq: GSE192740
Spatial transcriptomics: GSE192741
Murine APAP/CCL4
Our understanding of the functional heterogeneity of resident versus recruited macrophages in the diseased liver is limited. A population of recruited lipid associated macrophages (LAMs) has been reported to populate the diseased liver alongside resident Kupffer cells (KCs). However, the precise roles of these distinct macrophage subsets remain elusive. Here, using proteogenomics, we have identified LAMs in multiple models of liver injury. Moreover, we found that this phenotype is not specific to recruited macrophages, as a subset of resident KCs can also adopt a LAM-like phenotype in the mouse and human liver. By combining genetic mouse models targeting the distinct populations, we determined that both recruited LAMs and resident LAM-like KCs play crucial roles in tissue repair. Specifically, triggering receptor expressed on myeloid cells 2 (TREM2) expression on either resident or recruited macrophages is required for the efficient clearance of dying cells, enhancing repair and preventing exacerbated fibrosis.
https://www.cell.com/immunity/fulltext/S1074-7613(25)00002-0
Bulk RNA-Seq: GSE280652
Single Cell RNA-Seq: GSE280514
Spatial transcriptomics: GSE280515