ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2021
Single-Cell Transcriptome Analysis Uncovers Intratumoral Heterogeneity and Underlying Mechanisms for Drug Resistance in Hepatobiliary Tumor Organoids.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
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- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Organoids in cancer therapy: translational applications and clinical promise.Molecular cancer · 2026Review
- Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements.Journal of advanced research · 2026Review
- Identification and evaluation of glutamine-related gene characteristics based on multi-omics to predict the prognosis of patients with colorectal cancer.Journal of translational medicine · 2026Article
- Metabolic reprogramming and plasticity of cancer stem cells.Frontiers in cell and developmental biology · 2026Review
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Drug repurposing of sophoridine for sepsis-induced organ injury: from in-depth analysis of a single agent to a multi-target therapeutic paradigm.Frontiers in pharmacology · 2026Review
- Emodin triggers cuproptosis to suppress hepatocellular carcinoma via SLC7A11/FDX1 axis.Frontiers in oncology · 2026Article
- Individualized drug screening in cholangiocarcinoma using organoid models and patient-derived tumor xenograft.BMC cancer · 2025Article
- Therapeutic targeting of interleukin-17C signaling in carcinogenesis of endometriosis.Cell reports. Medicine · 2025Article
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- β-Hydroxybutyrate promotes chemoresistance and proliferation in breast cancer cells.Biochemistry and biophysics reports · 2025Article
- Integrative multi-omics and single-cell transcriptomics reveal ARHGEF12 driving chemoresistance in bladder cancer.Hereditas · 2025Article
- Single-cell multi-omics in biliary tract cancers: decoding heterogeneity, microenvironment, and treatment strategies.Molecular biomedicine · 2025Review
- Formulation Strategies for Immunomodulatory Natural Products in 3D Tumor Spheroids and Organoids: Current Challenges and Emerging Solutions.Pharmaceutics · 2025Review
- The application of liver cancer organoids in tumour precision medicine: A comprehensive review.iLIVER · 2025Review
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Molecular heterogeneity of hepatobiliary tumor including intertumoral and intratumoral disparity always leads to drug resistance. Here, seven hepatobiliary tumor organoids are generated to explore heterogeneity and evolution via single-cell RNA sequencing. HCC272 with high status of epithelia-mesenchymal transition proves broad-spectrum drug resistance. By examining the expression pattern of cancer stem cells markers (e.g., PROM1, CD44, and EPCAM), it is found that CD44 positive population may render drug resistance in HCC272. UMAP and pseudo-time analysis identify the intratumoral heterogeneity and distinct evolutionary trajectories, of which catenin beta-1 (CTNNB1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and nuclear paraspeckle assembly transcript 1 (NEAT1) advantage expression clusters are commonly shared across hepatobiliary organoids. CellphoneDB analysis further implies that metabolism advantage organoids with enrichment of hypoxia signal upregulate NEAT1 expression in CD44 subgroup and mediate drug resistance that relies on Jak-STAT pathway. Moreover, metabolism advantage clusters shared in several organoids have similar characteristic genes (GAPDH, NDRG1 (N-Myc downstream regulated 1), ALDOA, and CA9). The combination of GAPDH and NDRG1 is an independent risk factor and predictor for patient survival. This study delineates heterogeneity of hepatobiliary tumor organoids and proposes that the collaboration of intratumoral heterogenic subpopulations renders malignant phenotypes and drug resistance.
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