Heterogeneity and chimerism of endothelial cells revealed by single-cell transcriptome in orthotopic liver tumors.

Zhao, Qi, Molina-Portela, Maria Del Pilar, Parveen, Asma, Adler, Alexander, Adler, Christina, E, Hock, Wang, Wei, Ni, Min, Wei, Yi, Atwal, Gurinder, Mohrs, Markus, Thurston, Gavin, Eichten, Alexandra (November 2020) Heterogeneity and chimerism of endothelial cells revealed by single-cell transcriptome in orthotopic liver tumors. Angiogenesis, 23 (4). pp. 581-597. ISSN 0969-6970

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URL: https://www.ncbi.nlm.nih.gov/pubmed/32440964
DOI: 10.1007/s10456-020-09727-9

Abstract

The liver is a common host organ for cancer, either through lesions that arise in liver epithelial cells [e.g., hepatocellular carcinoma (HCC)] or as a site of metastasis by tumors arising in other organs (e.g., colorectal cancer). However, the changes that occur in liver stromal cells in response to cancer have not been fully characterized, nor has it been determined whether the different sources of liver cancer induce distinct stromal changes. Here, we performed single-cell profiling of liver stromal cells from mouse models of induced spontaneous liver cancer or implanted colorectal liver metastases, with a focus on tumor endothelial cells (ECs). While ECs in liver tissue adjacent to cancerous lesions (so-called adjacent normal) corresponded to liver zonation phenotypes, their transcriptomes were also clearly altered by the presence of a tumor. In comparison, tumor EC transcriptomes show stronger similarities to venous than sinusoidal ECs. Further, tumor ECs, independent of tumor origin, formed distinct clusters displaying conserved "tip-like" or "stalk-like" characteristics, similar to ECs from subcutaneous tumors. However, they also carried liver-specific signatures found in normal liver ECs, suggesting an influence of the host organ on tumor ECs. Our results document gene expression signatures in ECs in liver cancer and show that the host organ, and not the site of tumor origin (liver versus colorectal), is a primary determinant of EC phenotype. In addition, primarily in tumors, we further defined a cluster of chimeric cells that expressed both myeloid and endothelial cell markers and might play a role in tumor angiogenesis.

Item Type: Paper
Subjects: diseases & disorders > cancer > cancer types > liver cancer
Investigative techniques and equipment > assays > Single cell sequencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:
Communities: CSHL labs > Atwal lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: November 2020
Date Deposited: 06 May 2021 20:57
Last Modified: 06 May 2021 20:57
PMCID: PMC7525283
URI: https://repository.cshl.edu/id/eprint/40035

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