Abstract
Malignant cell growth is fueled by interactions between tumor cells and the stromal cells composing the tumor microenvironment. The human liver is a major site of tumors and metastases, but molecular identities and intercellular interactions of different cell types have not been resolved in these pathologies. Here, we apply single cell RNA-sequencing and spatial analysis of malignant and adjacent non-malignant liver tissues from five patients with cholangiocarcinoma or liver metastases. We find that stromal cells exhibit recurring, patient-independent expression programs, and reconstruct a ligand–receptor map that highlights recurring tumor–stroma interactions. By combining transcriptomics of laser-capture microdissected regions, we reconstruct a zonation atlas of hepatocytes in the non-malignant sites and characterize the spatial distribution of each cell type across the tumor microenvironment. Our analysis provides a resource for understanding human liver malignancies and may expose potential points of interventions.
Original language | English |
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Article number | e9682 |
Number of pages | 18 |
Journal | Molecular Systems Biology |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2020 |
Keywords
- human cell atlas
- liver cancer
- single cell RNAseq
- spatial transcriptomics
- tumor-stroma interactions
All Science Journal Classification (ASJC) codes
- General Immunology and Microbiology
- Applied Mathematics
- General Biochemistry,Genetics and Molecular Biology
- General Agricultural and Biological Sciences