ArticleCell death and differentiation2021
Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease.
Article in Cell death and differentiation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 107 citations in OpenAlex.
- RAB1A is a novel vulnerability in uveal melanoma revealed by dual inhibition of MNK1/2 and mTOR.Cell death and differentiation · 2026Article
- Transcription cofactor Hes6 interacts with Twist1 to facilitate EMT and promote gastric carcinogenesis by activating the PI3K/AKT signaling.Genes & diseases · 2026Article
- GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma.Cancer research · 2026Article
- Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms.Molecular systems biology · 2026Article
- Ephrin Receptors and Ephrin Ligands in Uveal Melanoma: A Big Data Analysis Using Web Resources.International journal of molecular sciences · 2025Article
- Interplay Between MicroRNAs and Breast Cancer Therapies: Personalized Therapeutic Potential for HER2-Low Breast Cancer.Cancers · 2025Review
- Characterization of Early Metastatic Subpopulations in Uveal Melanoma: Single-Cell Insights Into SPP1+ Cells and Their Interactions With Macrophages.Investigative ophthalmology & visual science · 2025Article
- SETDB1 is critically required for uveal melanoma growth and represents a promising therapeutic target.Cell death & disease · 2025Article
- CanCellCap: robust cancer cell capture across tissue types on single-cell RNA-seq data by multi-domain learning.BMC biology · 2025Article
- Integrating bulk and single-cell RNA sequencing reveals intratumor heterogeneity phenotypes and immune infiltration in pancreatic cancer.Discover oncology · 2025Article
- The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.Nature genetics · 2025Article
- Pan-cancer analysis reveals dual roles of HES6 in cancer immunity and prognosis.Discover oncology · 2025Article
- Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma.Current medicinal chemistry · 2025Article
- LHPP Attenuates Lipid Dysfunction of Uveal Melanoma by Relieving the Histidine Phosphorylation of ACO2.Research (Washington, D.C.) · 2025Article
- Microdissection of Distinct Morphological Regions Within Uveal Melanomas Identifies Novel Drug Targets.Cancers · 2024Article
- Single-cell and bulk transcriptome analysis reveals tumor cell heterogeneity and underlying molecular program in uveal melanoma.Journal of translational medicine · 2024Article
- Identification of feature genes and molecular mechanisms involved in cell communication in uveal melanoma through analysis of single‑cell sequencing data.Oncology letters · 2024Article
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- Immunotherapy response and resistance in patients with advanced uveal melanoma: a retrospective cohort study.Clinical and experimental medicine · 2024Article
- Article
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 1 country.
Funding
Abstract
Intratumor heterogeneity has been recognized in numerous cancers as a major source of metastatic dissemination. In uveal melanomas, the existence and identity of specific subpopulations, their biological function and their contribution to metastasis remain unknown. Here, in multiscale analyses using single-cell RNA sequencing of six different primary uveal melanomas, we uncover an intratumoral heterogeneity at the genomic and transcriptomic level. We identify distinct transcriptional cell states and diverse tumor-associated populations in a subset of the samples. We also decipher a gene regulatory network underlying an invasive and poor prognosis state driven in part by the transcription factor HES6. HES6 heterogenous expression has been validated by RNAscope assays within primary human uveal melanomas, which further unveils the existence of these cells conveying a dismal prognosis in tumors diagnosed with a favorable outcome using bulk analyses. Depletion of HES6 impairs proliferation, migration and metastatic dissemination in vitro and in vivo using the chick chorioallantoic membrane assay, demonstrating the essential role of HES6 in uveal melanomas. Thus, single-cell analysis offers an unprecedented view of primary uveal melanoma heterogeneity, identifies bona fide biomarkers for metastatic cells in the primary tumor, and reveals targetable modules driving growth and metastasis formation. Significantly, our findings demonstrate that HES6 is a valid target to stop uveal melanoma progression.
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