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Series GSE136103 Query DataSets for GSE136103
Status Public on Sep 12, 2019
Title Resolving the fibrotic niche of human liver cirrhosis using single-cell transcriptomics
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We profile the transcriptomes of over 100,000 human single cells, yielding molecular definitions for non-parenchymal cell types present in healthy and cirrhotic human liver. We uncover a novel scar-associated TREM2+CD9+ macrophage subpopulation, which expands in liver fibrosis, differentiates from circulating monocytes, has a corollary population in mouse liver fibrosis and is pro-fibrogenic. We also define novel ACKR1+ and PLVAP+ endothelial cells which expand in cirrhosis, are topographically scar-restricted and enhance leucocyte transmigration. Multi-lineage ligand-receptor modelling of interactions between the novel scar-associated macrophages, endothelial cells and PDGFRα+ collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides the conceptual framework required to discover rational therapeutic targets in liver cirrhosis.
 
Overall design Single-cell transcriptomic data are presented from 5 healthy livers, 5 cirrhotic livers and 4 PBMC samples from cirrhotic patients. We also present single-cell transcriptomic data on hepatic macrophages from healthy mice or mice following chronic carbon tetrachloride administration.
 
Contributor(s) Ramachandran P, Henderson NC, Wilson-Kanamori JR
Citation(s) 31597160
Submission date Aug 21, 2019
Last update date Oct 11, 2019
Contact name John Roger Wilson-Kanamori
Organization name University of Edinburgh
Department Centre for Inflammation Research
Lab Henderson / Ramachandran
Street address 47 Little France Crescent
City Edinburgh
ZIP/Postal code EH16 4TJ
Country United Kingdom
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (26)
GSM4041150 Healthy1_Cd45+
GSM4041151 Healthy1_Cd45-A
GSM4041152 Healthy1_Cd45-B
Relations
BioProject PRJNA561303
SRA SRP218975

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Supplementary file Size Download File type/resource
GSE136103_RAW.tar 416.0 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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