Fig. 6: ScRNA-Seq analyses of patient liver tissue uncover pro-inflammatory liver macrophages as nizatidine target.

a t-SNE map of single-cell transcriptomes from normal liver tissue of donors without history of chronic liver disease highlighting the main liver cell compartments. Data extracted from ref. ³⁵. Cells sharing similar transcriptome profiles are grouped by clusters and each dot represents one cell. Expression t-SNE map of HRH2, CLEC5A, CD163L1, and MARCO are shown. The color bar indicates Log2-normalized expression. b–e Perturbation of gene expression by nizatidine in liver tissue from patient with chronic liver disease and HCC identifies liver macrophages as therapeutic target. b Experimental approach. CD45⁺ leukocytes from patient liver tissue were enriched by flow cytometry and were treated with nizatidine or vehicle control (DMSO). Single cells were sorted and analyzed as described³⁵. c t-SNE map of single-cell transcriptomes showing control (blue) and nizatidine-treated cells (yellow), d the t-SNE map indicating the main cell compartments (MAFB: macrophages, CD8: CD8⁺ T lymphocytes). e Expression t-SNE map of HRH2, macrophage markers, and Siglec-10 are shown. The color bar indicates log2-normalized expression. f–h GSEA for differentially expressed genes between nizatidine-treated and CTRL macrophages depicted in d. f Normalized enrichment score (NES) of genes related to macrophage activation (classical M1 vs alternative M2). g NES of the pathways significantly enriched after nizatidine treatment (FDR ≤ 0.05). h Expression heatmap of differentially expressed genes in individual nizatidine- and control-treated macrophages. Each row representing a single cell. Markers of inflammation, fibrogenesis/cancer, and antigen presentation are shown. All genes are normalized by row from their own min to max (Log2 fold; p value ≤ 0.05). Source data are provided as a Source data file.