Resolving the fibrotic niche of human liver cirrhosis using single-cell transcriptomics
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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资源简介：
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.
提供机构：
University of Edinburgh
创建时间：
2022-02-20
