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. 2021 Sep 8;4:1049. doi: 10.1038/s42003-021-02562-8

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a Signaling pathways were predicted using CellChat to show interaction patterns between tumor subclusters and microenvironment cells. Four main patterns of ingoing and outgoing signals were identified, and associated pathways shown. b A network of signaling interactions of upregulated genes between tumor cell clusters and supporting tumor microenvironment cells shows crosstalk between cells in tumor. Gene–gene interactions were inferred using ToppCluster and interaction pairs between tumor cells and microenvironment cells were highlighted. Node size represents normalized expression levels of genes in each cell type. Node shape represents ligands (triangle) and receptors (circle). c Second harmonic generation (SHG) microscopy of tumor and background liver. Left to right, SHG (red—SHG, green—autofluorescence), KI67, and H&E staining demonstrates disorganized vessel structure in tumor samples. 20X Plan APO, 1024 × 1024 resolution, scale bar 50 µM. d Heatmaps and CellChat chord diagrams of upregulated pathways with indicated receptor/ligand interactions are highlighted. Extensive BMP, FGF, and CXCL signaling networks are shown. Lowly expressed genes in each pathway (maximal row values less than 0.5) were removed from the heatmap.