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 | American English |
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Article number | e9682 |
Journal | Molecular Systems Biology |
Volume | 16 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2020 |
Bibliographical note
Funding Information:We thank Liran Shlush, Itay Tirosh, Ravid Straussman, Lalit Kumar Dubey, Ronen Alon, and Rita Manco for valuable discussions. S.I. is supported by the Wolfson Family Charitable Trust, the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Helen and Martin Kimmel Institute for Stem Cell Research grant, the Minerva grant, the Israel Science Foundation grant No. 1486/16, the Broad Institute‐Israel Science Foundation grant No. 2615/18, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program grant No. 768956, the Chan Zuckerberg Initiative grant No. CZF2019‐002434, the Bert L. and N. Kuggie Vallee Foundation and the Howard Hughes Medical Institute (HHMI) international research scholar award. This research was supported by the Israeli Ministry Of Science and Technology (MOST) personal grant to H.M.
Funding Information:
We thank Liran Shlush, Itay Tirosh, Ravid Straussman, Lalit Kumar Dubey, Ronen Alon, and Rita Manco for valuable discussions. S.I. is supported by the Wolfson Family Charitable Trust, the Edmond de Rothschild Foundations, the Fannie Sherr Fund, the Helen and Martin Kimmel Institute for Stem Cell Research grant, the Minerva grant, the Israel Science Foundation grant No. 1486/16, the Broad Institute-Israel Science Foundation grant No. 2615/18, the European Research Council (ERC) under the European Union?s Horizon 2020 research and innovation program grant No. 768956, the Chan Zuckerberg Initiative grant No. CZF2019-002434, the Bert L. and N. Kuggie Vallee Foundation and the Howard Hughes Medical Institute (HHMI) international research scholar award. This research was supported by the Israeli Ministry Of Science and Technology (MOST) personal grant to H.M.
Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY 4.0 license
Keywords
- human cell atlas
- liver cancer
- single cell RNAseq
- spatial transcriptomics
- tumor-stroma interactions