ArticleProceedings of the National Academy of Sciences of the United States of America2021
Volumetric compression develops noise-driven single-cell heterogeneity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Article
- Article
- Volumetric mechanoplasticity couples melanoma drug tolerance to susceptibility to CD8bioRxiv : the preprint server for biology · 2026Article
- Large-Scale Bioprinting of Human Epiblast-Like Models Featuring Disc-Shaped Morphogenesis and Gastrulation Events.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adaptation to Volumetric Compression Drives an Apoptosis-Resistant and Invasive Phenotype in Liver Cancer.Cancer research · 2025Article
- Review
- Review
- Mechanical Cell Reprogramming on Tissue-Mimicking Hydrogels for Cancer Cell Transdifferentiation.Research (Washington, D.C.) · 2025Article
- Spatially defined microenvironment for engineering organoids.Biophysics reviews · 2024Review
- Gene choice in cancer cells is exclusive in ion transport but concurrent in DNA replication.Computational and structural biotechnology journal · 2024Article
- Integration of single-cell sequencing and bulk transcriptome data develops prognostic markers based on PCLAFHeliyon · 2024Article
- Compressive stresses in cancer: characterization and implications for tumour progression and treatment.Nature reviews. Cancer · 2024Review
- Microscopy methods to visualize nuclear organization in biomechanical studies.Current opinion in biomedical engineering · 2024Article
- Bridging the organoid translational gap: integrating standardization and micropatterning for drug screening in clinical and pharmaceutical medicine.Life medicine · 2024Review
- Cancer spreading patterns based on epithelial-mesenchymal plasticity.Frontiers in cell and developmental biology · 2024Article
- Compression drives diverse transcriptomic and phenotypic adaptations in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Enhancing single-cell biology through advanced AI-powered microfluidics.Biomicrofluidics · 2023Article
- Population dynamics of EMT elucidates the timing and distribution of phenotypic intra-tumoral heterogeneity.iScience · 2023Article
- Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia.BMC cancer · 2023Article
- Dynamics of Epithelial-Mesenchymal Plasticity: What Have Single-Cell Investigations Elucidated So Far?ACS omega · 2023Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Recent studies have revealed that extensive heterogeneity of biological systems arises through various routes ranging from intracellular chromosome segregation to spatiotemporally varying biochemical stimulations. However, the contribution of physical microenvironments to single-cell heterogeneity remains largely unexplored. Here, we show that a homogeneous population of non-small-cell lung carcinoma develops into heterogeneous subpopulations upon application of a homogeneous physical compression, as shown by single-cell transcriptome profiling. The generated subpopulations stochastically gain the signature genes associated with epithelial-mesenchymal transition (EMT; VIM, CDH1, EPCAM, ZEB1, and ZEB2) and cancer stem cells (MKI67, BIRC5, and KLF4), respectively. Trajectory analysis revealed two bifurcated paths as cells evolving upon the physical compression, along each path the corresponding signature genes (epithelial or mesenchymal) gradually increase. Furthermore, we show that compression increases gene expression noise, which interplays with regulatory network architecture and thus generates differential cell-fate outcomes. The experimental observations of both single-cell sequencing and single-molecule fluorescent in situ hybridization agrees well with our computational modeling of regulatory network in the EMT process. These results demonstrate a paradigm of how mechanical stimulations impact cell-fate determination by altering transcription dynamics; moreover, we show a distinct path that the ecology and evolution of cancer interplay with their physical microenvironments from the view of mechanobiology and systems biology, with insight into the origin of single-cell heterogeneity.
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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.