Table 3.
Key findings related to malignant cell heterogeneity among tumors obtained using single-cell sequencing
| Tumor | Technology | Platform | Key findings | References |
|---|---|---|---|---|
| PDAC | scRNA-seq, trajectory analysis | 10X Genomics | Identified 11 subpopulations of malignant tumor cells, including a subset of malignant ductal cells with unique proliferative features associated with the inactivation of tumor-infiltrating T cells | [90] |
| PDAC | scRNA-seq, trajectory analysis | 10X Genomics | Identified 6 acinar metaplastic cell subpopulations during the progression from preinvasive stages to tumor formation in a mouse model | [212] |
| LUAD, LUSC | Bulk and scRNA-seq | 10X Genomics | Revealed that nongenetic heterogeneity is a major predictor of phenotypic heterogeneity | [78] |
| LUAD | scRNA-seq | 10X Genomics | Identified 19 tumor-specific markers as candidate markers for the detection of extraordinarily rare circulating tumor cells | [213] |
| lung cancer | Single-cell sequencing | CyTOF | Revealed that AXL inhibition suppresses SMAD4/TGFβ signaling and induces JAK1/STAT3 signaling pathways, and AXL functions via CD133-mediated cancer stemness and hybrid EMT features in patients with advanced-stage tumors | [214] |
| GGN-ADC, SADC | scRNA-seq, flow cytometry | 10X Genomics | Revealed the downregulation of signaling pathways associated with angiogenesis and cell proliferation, low expression of collagens of fibroblasts and activated immune cells in GGN-ADC | [215] |
| melanoma | scRNA-seq, bulk RNA-seq, ATAC-seq | 10X Genomics | Confirmed the intermediate state of melanoma cells, which is governed by SOX6, NFATC2, EGR3, ELF1 and ETV4 and regulated by a gene regulatory network | [79] |
| GA | scRNA-seq | 10X Genomics | Identified 5 subtypes of malignant tumor cells, 3 of which corresponded with the histopathological features of Lauren’s subtypes, while 1 was associated with the GA-FG-CCP | [216] |
| EGC | scRNA-seq | 10X Genomics | Revealed that the glandular mucous cells tended to acquire an intestinal-like stem cell phenotype during metaplasia; HSE6 may help identify early-stage tumors | [216] |
| AML | scRNA-seq, next-generation sequencing | 10X Genomics | Identified 3 leukemia subpopulations arrested at different stages of myeloid differentiation: CD34*CD117dim blasts (blocked in G0/G1 phase), CD34*CD117bri blasts and partial maturation myeloid cells | [217] |
| MM | scRNA-seq | Fluidigm C1 | Identified 4 groups of malignant cells; the L1 group from MGUS expressed the lowest levels of genes involved in oxidative phosphorylation, while the L4 group from MM displayed the highest expression | [218] |
| NEPC | scRNA-seq | 10X Genomics | Revealed that focal neuroendocrine differentiation exclusively originates from luminal-like malignant cells and identified differentiation-association signature genes | [219] |
| medulloblastoma | scRNA-seq | 10X Genomics | Identified OLIG2-expressing glial progenitors as transit-amplifying cells at tumor onset, and they are enriched in therapy-resistant and recurrent medulloblastoma | [220] |
| glioma | scRNA-seq | 10X Genomics | Identified Zfp36l1 as a key gene for glioma growth, various transitional intermediate states and corresponding developmental lineages | [221] |
| glioblastoma | scRNA-seq | 10X Genomics | Identified key genes involved in NSC transformation into tumor-promoting cells; NSCs may promote metastasis via extracellular vesicles | [222] |
| glioblastoma | scRNA-seq | 10X Genomics | Identified RAD51AP1 as an independent prognostic factor and a potent mediator of EGFRvlll signaling | [223] |
| ESCC | scRNA-seq, bulk sequencing | SMART-Seq 2 | Identified genes associated with radioresistance, including autophagy-related 9B, DNA damage-inducible transcript 4, myoglobin and plasminogen activator tissue type | [224] |
| HCC | scRNA-seq | 10X Genomics | Identified the involvement of JUNB, a pro-oncogene, in the immune response and progression of HCC | [225] |
| HCC | Single-cell mass cytometry, RNA sequencing | Fluidigm | Revealed that the lncRNA HOXA-AS2 is associated with the regulation of cancer stemness during tumorigenesis and poor prognosis; identified an EPCAM + C-MYC + CK19 subpopulation in HOXA-AS2 high patients | [226] |
| breast cancer | scRNA-seq | Hydro-Seq | Revealed that CAFs increase cancer stemness and alter the epithelial/mesenchymal status during coculture with malignant cells | [111] |
| breast cancer | Single-cell whole-exome sequencing | Fluidigm C1 | Revealed the evolutionary process of cells with SNVs in hit driver genes via CNVs acquired in chromosomal regions; identified the Plekha5 gene as a suppressor of tumor metastasis | [227] |
PDAC: pancreatic ductal adenocarcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; GGN-ADC: ground glass nodule adenocarcinoma; SADC: solid adenocarcinoma; GA: gastric adenocarcinoma; GA-FG-CCP: fundic gland-type gastric adenocarcinoma; AML: acute myelogenous leukemia; NEPC: neuroendocrine prostate cancer; EGC: early gastric cancer; ESCC: esophageal squamous cell carcinoma; MM: multiple myeloma; HCC: hepatocellular carcinoma; ESCC: esophageal squamous cell carcinoma