Table 2. Overview of recent studies on human liver disease at the single-cell level.
| Liver diseases | Samples | Patients | Methods | Synopsis | Year | Ref. |
|---|---|---|---|---|---|---|
| Hepatitis | Huh7.5-NTCP cells | none | scRNA-seq(Illumina HiSeq PE150); CRISPR-Cas9 | Rare transcripts from HBV-infected hepatocytes are preferentially enriched; HBV infection did not significantly alter gene expression but treatment with IFN-α altered gene expression in Huh7.5-NTCP cells | 2021 | 50 |
| Peripheral blood | 12 | scATAC-seq | Identified 12 leukocytic clusters corresponding to five cell types; specific cell type of CHB was B-0 and T-3 | 2022 | 51 | |
| NASH liver tissue | 10 | scRNA-seq (10×) | Cell type-specific transcriptional features of NASH; two distinct populations of activated hepatic stellate cells associated with fibrosis levels | 2022 | 56 | |
| Liver fibrosis / Cirrhosis | Healthy, cirrhotic liver tissue; peripheral blood | 10 | scRNA-seq (10×) | Characterizing and comparing the functional diversity of liver biopsy cells from human fibrotic and normal livers; identified scar-associated TREM2+CD9+macrophages, ACKR1+ and PLVAP+ endothelial cells | 2019 | 52 |
| Healthy, HBV-related cirrhosis, alcoholic cirrhosis liver tissue | 15 | scRNA-seq (Illumina HiSeq X) | Different immune profiles between alcoholic and HBV cirrhotic patients; Galectin-9 may be a potential therapeutic target for alcoholic cirrhosis treatment | 2023 | 53 | |
| ACLF | Healthy, cirrhosis, ACLF liver tissue | 25 | scRNA-seq (Illumina HiSeq X) | Revealed the state of hepatic lymphatic endothelial cells in hepatitis B virus-associated ACLF; monocytes/macrophages infiltrate into ACLF | 2022 | 54 |
| HCC | HCC tumor tissue | 8 | scRNA-seq (10×) | Cellular heterogeneity in HCC; intertumoral heterogeneity higher than intratumor heterogeneity; immunocyte characteristics | 2021 | 57 |
| HCC tumor tissue | 1 | scRNA-seq (SMART- seq) | Heterogeneity of CSCs in human HCC; identified CSCs as CD24+/CD133+/EpCAM+/CD45- cells | 2018 | 58 | |
| HCC tumor tissue; normal liver tissue; peripheral blood | 8 | scRNA-seq (Illumina HiSeq) | Characteristics of immune cell in HCC; revealed specific cytokines/compartmental factors | 2019 | 59 | |
| HCC, iCCA tumor tissue | 7 | scRNA-seq (10×) | Similar developmental trajectories in the same tumor, but heterogeneity in stemness gene expression | 2022 | 60 | |
| HCC Tumor tissue; normal liver tissue; peripheral blood | 6 | scRNA-seq (Illumina HiSeq) | Identified 11 populations of T cells in HCC; TME; exhausted CD8+T cells and Tregs preferentially enriched in HCC | 2017 | 55 | |
| HCC tumor tissue; normal liver tissue | 18 | scRNA-seq (10×) | Immune characteristics in early-relapse HCC; early-relapse tumors have less regulatory T cells, DCs and increased infiltrating CD8+T cells and higher expressed CD161+CD8+T cell compared to the primary tumors | 2021 | 61 | |
| (HCC, iCCA, HH, CHC, ASC, SAR, SLC) Tumor tissue; normal liver tissue; peripheral blood | 124 | scRNA-seq (Illumina HiSeq) | Identified six tumor-associated neutrophils, among them CCL4+ TAN and PD-L1+ TAN could promote tumor growth | 2022 | 62 |
ACLF, acute-on-chronic liver failure; ACKR1, atypical chemokine receptor 1; ASC, adenosquamous carcinoma; CCL4, C-C motif chemokine ligand 4; CHB, chronic hepatitis B; CHC, combined hepatocellular-cholangiocarcinoma; CSCs, cancer stem cells; DCs, dendritic cells; EpCAM, epithelial cell adhesion molecule; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HH, hepatic hemangioma; iCCA, intrahepatic cholangiocarcinoma; IFN-α, interferon-α; NASH, nonalcoholic steatohepatitis; PD-L1, programmed cell death-ligand 1; PLVAP, plasmalemma vesicle-associated protein; SAR, sarcomatoid carcinoma; scATAC-seq, single-cell assay for transposase-accessible chromatin with high throughput sequencing; scRNA-seq, single-cell transcriptome sequencing; SLC, secondary liver cancer; TAN, tumors-associated neutrophil; TME, tumor microenvironment; TREM2, triggering receptor expressed on myeloid cells-2.