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| 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.
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| 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.
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| Contributor(s) |
Ramachandran P, Henderson NC, Wilson-Kanamori JR |
| Citation(s) |
31597160, 31722201, 34887405 |
| |
| Submission date |
Aug 21, 2019 |
| Last update date |
Jan 10, 2022 |
| Contact name |
John Roger Wilson-Kanamori |
| Organization name |
University of Edinburgh
|
| Department |
Centre for Inflammation Research
|
| Lab |
Henderson
|
| Street address |
47 Little France Crescent
|
| City |
Edinburgh |
| ZIP/Postal code |
EH16 4TJ |
| Country |
United Kingdom |
| |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA561303 |
| SRA |
SRP218975 |
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