ArticleBMC biology2021
Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.
Article in BMC biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 35 citations in OpenAlex.
- Spatial Transcriptomics Analysis of Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Epigenetic modification of cuproptosis by non-coding RNAs in cancer drug resistance.Molecular cancer · 2025Review
- PreDigs: A Database of Context-specific Cell Type Markers and Precise Cell Subtypes for Digestive Cell Annotation.Genomics, proteomics & bioinformatics · 2025Article
- Single-cell multi-omics in the study of digestive system cancers.Computational and structural biotechnology journal · 2024Review
- Joint analysis of mutational and transcriptional landscapes in human cancer reveals key perturbations during cancer evolution.Genome biology · 2024Article
- Innovative aspects and applications of single cell technology for different diseases.American journal of cancer research · 2024Review
- Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.Frontiers in immunology · 2024Article
- Tumor organoid model of colorectal cancer (Review).Oncology letters · 2023Review
- Artificial Intelligence-Assisted Transcriptomic Analysis to Advance Cancer Immunotherapy.Journal of clinical medicine · 2023Review
- Organoids for Modeling (Colorectal) Cancer in a Dish.Cancers · 2022Review
- Intestinal cellular heterogeneity and disease development revealed by single-cell technology.Cell regeneration (London, England) · 2022Review
- Review
- Odontogenic MSC Heterogeneity: Challenges and Opportunities for Regenerative Medicine.Frontiers in physiology · 2022Review
- Capturing tumour heterogeneity in pre- and post-chemotherapy colorectal cancer ascites-derived cells using single-cell RNA-sequencing.Bioscience reports · 2021Article
- Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.BMC biology · 2021Article
- The current landscape of single-cell transcriptomics for cancer immunotherapy.The Journal of experimental medicine · 2021Review
- Tumor heterogeneity in muscle-invasive bladder cancer.Translational andrology and urology · 2020Review
- Single Cell Transcriptome in Colorectal Cancer-Current Updates on Its Application in Metastasis, Chemoresistance and the Roles of Circulating Tumor Cells.Frontiers in pharmacology · 2020Review
- Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis.Cancer control : journal of the Moffitt Cancer CenterArticle
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling.
resultsWe performed single-cell exome and transcriptome sequencing of 200 cells to investigate how ITH is generated in a mouse colorectal cancer model. In the model, a single normal intestinal cell is grown into organoids that mimic the intestinal crypt structure. Upon RNAi-mediated downregulation of a tumor suppressor gene APC, the transduced organoids were serially transplanted into mice to allow exposure to in vivo microenvironments, which play relevant roles in cancer development. The ITH of the transcriptome increased after the transplantation, while that of the exome decreased. Mutations generated during organoid culture did not greatly change at the bulk-cell level upon the transplantation. The RNA ITH increase was due to the emergence of new transcriptional subpopulations. In contrast to the initial cells expressing mesenchymal-marker genes, new subpopulations repressed these genes after the transplantation. Analyses of colorectal cancer data from The Cancer Genome Atlas revealed a high proportion of metastatic cases in human subjects with expression patterns similar to the new cell subpopulations in mouse. These results suggest that the birth of transcriptional subpopulations may be a key for adaptation to drastic micro-environmental changes when cancer cells have sufficient genetic alterations at later tumor stages.
conclusionsThis study revealed an evolutionary dynamics of single-cell RNA and DNA heterogeneity in tumor progression, giving insights into the mesenchymal-epithelial transformation of tumor cells at metastasis in colorectal cancer.
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