A single cell atlas of the human liver tumor microenvironment

Hassan Massalha, Keren Bahar Halpern, Samir Abu-Gazala, Tamar Jana, Efi E. Massasa, Andreas E. Moor, Lisa Buchauer, Milena Rozenberg, Eli Pikarsky, Ido Amit, Gideon Zamir, Shalev Itzkovitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations


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 languageAmerican English
Article numbere9682
JournalMolecular Systems Biology
Issue number12
StatePublished - Dec 2020

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY 4.0 license


  • human cell atlas
  • liver cancer
  • single cell RNAseq
  • spatial transcriptomics
  • tumor-stroma interactions


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