期刊
MOLECULAR SYSTEMS BIOLOGY
卷 16, 期 12, 页码 -出版社
WILEY
DOI: 10.15252/msb.20209682
关键词
human cell atlas; liver cancer; single cell RNAseq; spatial transcriptomics; tumor‐ stroma interactions
资金
- Wolfson Family Charitable Trust
- Edmond de Rothschild Foundations
- Fannie Sherr Fund
- Helen and Martin Kimmel Institute for Stem Cell Research
- Minerva grant
- Israel Science Foundation [1486/16]
- Broad Institute-Israel Science Foundation [2615/18]
- European Research Council (ERC) under the European Union [768956]
- Chan Zuckerberg Initiative [CZF2019-002434]
- Bert L. and N. Kuggie Vallee Foundation
- Howard Hughes Medical Institute (HHMI)
- Israeli Ministry Of Science and Technology (MOST)
- European Research Council (ERC) [768956] Funding Source: European Research Council (ERC)
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.
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