ArticleNature communications2019
Role of network-mediated stochasticity in mammalian drug resistance.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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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
51 citing papers in PubMed, 96 citations in OpenAlex.
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- Mammalian synthetic gene circuits for biopharmaceutical development & manufacture.NPJ systems biology and applications · 2025Review
- A memory-driven reinforcement learning model of phenotypic adaptation for anticipating therapeutic resistance in prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Reprogramming the tumor microenvironment with c-MYC-based gene circuit platform to enhance specific cancer immunotherapy.Nature communications · 2025Article
- Cyclo-stationary distributions of mRNA and Protein counts for random cell division times.bioRxiv : the preprint server for biology · 2025Article
- Stochastic gene expression in proliferating cells: Differing noise intensity in single-cell and population perspectives.PLoS computational biology · 2025Article
- Gene choice in cancer cells is exclusive in ion transport but concurrent in DNA replication.Computational and structural biotechnology journal · 2024Article
- Optimizing a CRISPR-Cas13d Gene Circuit for Tunable Target RNA Downregulation with Minimal Collateral RNA Cutting.ACS synthetic biology · 2024Article
- Synthetic gene circuit evolution: Insights and opportunities at the mid-scale.Cell chemical biology · 2024Review
- Histone deacetylase Hos2 regulates protein expression noise by potentially modulating the protein translation machinery.Nucleic acids research · 2024Article
- Stochastic Gene Expression in Proliferating Cells: Differing Noise Intensity in Single-Cell and Population Perspectives.bioRxiv : the preprint server for biology · 2024Article
- Contributions of transcriptional noise to leukaemia evolution: KAT2A as a case-study.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Adaptive DNA amplification of synthetic gene circuit opens a way to overcome cancer chemoresistance.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Optimal phenotypic adaptation in fluctuating environments.Biophysical journal · 2023Article
- Deep-learning-assisted Sort-Seq enables high-throughput profiling of gene expression characteristics with high precision.Science advances · 2023Article
- Evolutionary innovation through transcription factor rewiring in microbes is shaped by levels of transcription factor activity, expression, and existing connectivity.PLoS biology · 2023Article
- Quantitative systems-based prediction of antimicrobial resistance evolution.NPJ systems biology and applications · 2023Review
- MaxCal can infer models from coupled stochastic trajectories of gene expression and cell division.Biophysical journal · 2023Article
- Nonmonotone invasion landscape by noise-aware control of metastasis activator levels.Nature chemical biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
A major challenge in biology is that genetically identical cells in the same environment can display gene expression stochasticity (noise), which contributes to bet-hedging, drug tolerance, and cell-fate switching. The magnitude and timescales of stochastic fluctuations can depend on the gene regulatory network. Currently, it is unclear how gene expression noise of specific networks impacts the evolution of drug resistance in mammalian cells. Answering this question requires adjusting network noise independently from mean expression. Here, we develop positive and negative feedback-based synthetic gene circuits to decouple noise from the mean for Puromycin resistance gene expression in Chinese Hamster Ovary cells. In low Puromycin concentrations, the high-noise, positive-feedback network delays long-term adaptation, whereas it facilitates adaptation under high Puromycin concentration. Accordingly, the low-noise, negative-feedback circuit can maintain resistance by acquiring mutations while the positive-feedback circuit remains mutation-free and regains drug sensitivity. These findings may have profound implications for chemotherapeutic inefficiency and cancer relapse.
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Registered trials
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.