Fig. 1: Three functional archetypes of HCC cancer cells.

A Schematic diagram of this study design. B UMAP (uniform manifold approximation and projection) of main cell types in human primary HCC sc & snRNA-seq dataset (left) and mouse HCC scRNA-seq dataset (right). C Hierarchical clustering of pairwise similarities between NMF programs identified across all cancer cells from snRNA-seq samples. D Heatmap displays the Pearson correlation coefficients calculated between the single-cell gene signature scores of NMF metaprograms. E Heatmap showing the expression of NMF metaprograms. Cells were ordered by the P2 score. F PCA of 1000 random-sampled cancer cells colored by functional archetypes (left). The normalized, scaled expression of indicated marker genes for each functional archetype (right). G, J HE staining and predicted abundance of indicated cancer cell archetypes in spatial sections of HCC-2 (G) and HCC-3 (J). Data are representative of n = 4 spatial transcriptomic slides. Scale bar, 1 mm. H, K Volcano plot displays the DEGs between indicated spatial regions in HCC-2 (H) and HCC-3 (K). I, L GO analysis of the DEGs of indicated spatial regions in HCC-2 (I) and HCC-3 (L). M Immunofluorescence staining of CD44, APOE, SAA1/2, and PanCK on HCC sections. For each field, representative cells are indicated by arrows, including CD44⁺PanCK⁺ cells (red), APOE⁺PanCK⁺ cells (yellow), and SAA1/2⁺PanCK⁺ cells (green). Scale bar, 50 μm. Images are representative of n = 3 HCC samples. Schematic in A was created in BioRender. Chu, T. (2025) https://BioRender.com/r2v4jgs.