Table 2.

Key findings related to tumor heterogeneity among various tumors using scRNA-seq

Tumor	Year	Species	Protocol	Accession number (custom database if available)	Key findings	References
Lung cancer	2020	Human	10 × Genomics	EGAD00001005054	Identified a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage, and revealed potential diagnostic and therapeutic targets in cancer-microenvironment interactions	[156]
	2020	Human	Smart-seq2	NCBI BioProject #PRJNA591860	Identified that individual tumors and cancer cells exhibit substantial molecular diversity and that tumor microenvironment cells exhibit marked therapy-induced plasticity	[157]
	2022	Human	STRT-seq	HRA000270	Provided novel insights into the tumor heterogeneity of NSCLC in terms of the identification of prevalent mixed-lineage subpopulations of cancer cells with combined SCC, ADC, and NET signatures and offered clues for potential treatment strategies in these patients	[158]
Gastric cancer	2020	Human	10 × Genomics	PRJEB40416	Highlighted response heterogeneity within MSI-H gastric cancer treated with pembrolizumab monotherapy; supported the potential of extended baseline and early on-treatment biomarker analyses to identify responders	[95]
	2021	Human	10 × Genomics	EGAS00001004443	The links between tumor cell lineage/state and ITH were illustrated at the transcriptome, genotype, molecular, and phenotype levels	[72]
	2021	Human	10 × Genomics	HRA000051	A panel of differentiation-related genes revealed large differences in differentiation degree within and between tumors	[80]
Liver cancer	2022	Human	Seq-Well S3	GSE186975	Identified five hepatoblastoma tumor signatures that may account for the tumor heterogeneity observed in this disease, and used patient-derived hepatoblastoma spheroid cultures to predict differential responses to treatment based on the transcriptomic signature of each tumor	[237]
Esophageal cancer	2022	Human	10 × Genomics	GSE196756	Revealed intratumoral and intertumoral epithelium heterogeneity and tremendous differences between the tumor and normal epithelium. Epithelium cells and myeloid cells had more frequent cell‒cell communication than epithelium cells and T cells	[238]
	2021	Human	10 × Genomics	PRJNA777911	Uncovered heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments	[86]
Melanoma	2016	Human	Smart-seq2	DUOS-000002; GSE72056	Malignant cells within the same tumor displayed heterogeneity in the transcription of proteins related to the cell cycle, spatial context, and drug resistance program	[239]
	2020	Human	10 × Genomics	GSE139829	Analysis of tumor cells revealed previously unappreciated subclonal genomic complexity and transcriptional states	[94]
	2021	Human	10 × Genomics	GSE138665	Uncovered intratumoral heterogeneity at the genome and transcriptome level	[81]
Acute lymphoblastic leukemia	2020	Human	10 × Genomics	GSE132509	The predicted developmental states of cancer cells were inversely correlated with the expression levels of ribosomal protein, which could be a common contributor to intraindividual heterogeneity in childhood ALL patients	[240]
Diffuse large B cell lymphoma	2022	Human	10 × Genomics	CNGBdb: CNP0001940	High intratumor and intertumor heterogeneity was identified in DLBCL	[216]
	2022	Human	10 × Genomics	https://heidata.uniheidelberg.de	Provided an in-depth dissection of the transcriptional features of malignant B cells and the TME in DLBCL and new insights into DLBCL heterogeneity	[229]
Primary central nervous system lymphoma	2021	Human	10 × Genomics	GEO: GSE181304	Different subtypes of T cells and DCs showed significant heterogeneity	[85]
B-cell lymphoma	2020	Human	10 × Genomics	https://heidata.uni-heidelberg.de	Malignant subpopulations from the same patient responded strikingly differently to anticancer drugs ex vivo, highlighting the relevance of intratumor heterogeneity for personalized cancer therapy	[241]
Cutaneous T cell lymphoma	2018	Human	BD Precise assay	Correspondence with authors	Patients with SS displayed a high degree of single-cell heterogeneity within the malignant T-cell population, and the distinct subpopulation of malignant T cells exhibited HDACi resistance	[76]
	2019	Human	10 × Genomics	GSE128531	Provided an unprecedented view of lymphocyte heterogeneity and identifying tumor-specific molecular signatures, with important implications for diagnosis and personalized disease treatment	[77]
	2021	Human	10 × Genomics	GSE171811	Striking subclonal molecular heterogeneity was observed within clonal malignant T-cell populations in the skin and blood of patients with leukemic CTCL. The tissue microenvironment influenced the transcriptional state of malignant T cells, likely contributing to the evolution of malignant clones	[242]
	2022	Human	10 × Genomics	GSA-Human: HRA000166	Revealed the intratumor and interlesion diversity of CTCL patients, proposed a multistep tumor evolution model that further established a novel subtype, the TCyEM group with a cytotoxic effector memory T-cell phenotype, and identified increased M2 macrophage infiltration	[78]
Subcutaneous panniculitis-like T cell lymphoma	2021	Human	10 × Genomics	GSA-Human: HRA000370	Provided insights into the heterogeneity of subcutaneous panniculitis-like T-cell lymphoma, as well as a better understanding of the transcription characteristics and immune microenvironment of this rare tumor	[208]