ArticleNature communications2018
Longitudinal single-cell RNA sequencing of patient-derived primary cells reveals drug-induced infidelity in stem cell hierarchy.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 174 citations in OpenAlex.
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- Integrating Mutation-Derived and Expression Features from Single-Cell RNA Sequencing: Pitfalls of Standard Cross-Validation in Small-Cohort Settings.International journal of molecular sciences · 2026Article
- Whole transcriptome sequencing and ceRNA regulatory network in diabetic peripheral neuropathy.Scientific reports · 2026Article
- scRADAR: Dissecting intratumoral drug response heterogeneity at single-cell resolution via mechanism-guided prototype routing.PLoS computational biology · 2026Article
- A human patient-derived organoid biobank to model tumor heterogeneity and therapeutic vulnerability for oral squamous cell carcinoma.Cell reports. Medicine · 2026Article
- Epigenetic reprogramming in multiple myeloma-Challenges and opportunities.International journal of cancer · 2026Review
- scXDR: drug response prediction across single-cell datasets via heterogeneous network transfer learning.Communications biology · 2026Article
- Multi-omics Approaches to CCAAT/Enhancer-Binding Protein Beta in Oral Squamous Cell Carcinoma: Crosstalk Between Tumor Cells and Tumor-Associated Macrophages Driving Disease Progression.Current cancer drug targets · 2026Article
- CellDuality: Unlocking Biological Reasoning in LLMs with Self-Supervised RLVR.... International Conference on Learning Representations · 2026Article
- Longitudinal omics data analysis: approaches and applications.Computational and structural biotechnology journal · 2026Review
- Integrin-mediated SPP1 signaling from macrophages orchestrates extracellular matrix remodeling and chondrogenesis in heterotopic ossification.Journal of translational medicine · 2025Article
- Unlocking Cellular Memory and Gene Regulatory Networks: Pioneering the Future of Therapeutic Innovations.Cells · 2025Article
- Resistance to anti-LAG-3 plus anti-PD-1 therapy in head and neck cancer is mediated by Sox9+ tumor cells interaction with Fpr1+ neutrophils.Nature communications · 2025Article
- CAN-Scan: A multi-omic phenotype-driven precision oncology platform identifies prognostic biomarkers of therapy response for colorectal cancer.Cell reports. Medicine · 2025Article
- Identification of drug-resistant individual cells within tumors by semi-supervised transfer learning from bulk to single-cell transcriptome.Communications biology · 2025Article
- Expression analysis of SOX2 and SOX9 in patients with oral squamous cell carcinoma.Head & neck · 2025Article
- Single-nucleus CUT&RUN elucidates the function of intrinsic and genomics-driven epigenetic heterogeneity in head and neck cancer progression.Genome research · 2025Article
- DrugFormer: Graph-Enhanced Language Model to Predict Drug Sensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- scDTL: enhancing single-cell RNA-seq imputation through deep transfer learning with bulk cell information.Briefings in bioinformatics · 2024Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemo-resistance is one of the major causes of cancer-related deaths. Here we used single-cell transcriptomics to investigate divergent modes of chemo-resistance in tumor cells. We observed that higher degree of phenotypic intra-tumor heterogeneity (ITH) favors selection of pre-existing drug-resistant cells, whereas phenotypically homogeneous cells engage covert epigenetic mechanisms to trans-differentiate under drug-selection. This adaptation was driven by selection-induced gain of H3K27ac marks on bivalently poised resistance-associated chromatin, and therefore not expressed in the treatment-naïve setting. Mechanistic interrogation of this phenomenon revealed that drug-induced adaptation was acquired upon the loss of stem factor SOX2, and a concomitant gain of SOX9. Strikingly we observed an enrichment of SOX9 at drug-induced H3K27ac sites, suggesting that tumor evolution could be driven by stem cell-switch-mediated epigenetic plasticity. Importantly, JQ1 mediated inhibition of BRD4 could reverse drug-induced adaptation. These results provide mechanistic insights into the modes of therapy-induced cellular plasticity and underscore the use of epigenetic inhibitors in targeting tumor evolution.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.