Volumetric compression develops noise-driven single-cell heterogeneity
Name
zhao-et-al-2021-volumetric-compression-develops-noise-driven-single-cell-heterogeneity.pdf
Description
Published version
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2.41 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Zhao, Xing
Hu, Jiliang
Li, Yiwei
Guo, Ming
Date Issued
December 21, 2021
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
Zhao, Xing, Hu, Jiliang, Li, Yiwei and Guo, Ming. 2021. "Volumetric compression develops noise-driven single-cell heterogeneity." Proceedings of the National Academy of Sciences, 118 (51).
Version
Final published version
Abstract
Significance
Tumor heterogeneity is widely attributed to the imperfection of DNA replication. However, little is known about the mechanoregulation of tumor heterogeneity. Here, we report that volumetric compression that usually arises from tumor progression increases the overall gene-expression noise, leading to differential cell-fate transitions along epithelial/mesenchymal transition regulatory network from homogeneous non–small-cell lung carcinoma. The increased noise could be caused by a transit decrease in gene expression following the decreasing cell volume under compression. Both the experiments and numerical modeling confirmed the differential cell-fate transitions from the hybrid epithelial/mesenchymal state to either epithelial or mesenchymal states stochastically. Thus, we suggest that the cause of tumor heterogeneity could be its mechanical microenvironment as sensed by its cytoplasmic volume.
Tumor heterogeneity is widely attributed to the imperfection of DNA replication. However, little is known about the mechanoregulation of tumor heterogeneity. Here, we report that volumetric compression that usually arises from tumor progression increases the overall gene-expression noise, leading to differential cell-fate transitions along epithelial/mesenchymal transition regulatory network from homogeneous non–small-cell lung carcinoma. The increased noise could be caused by a transit decrease in gene expression following the decreasing cell volume under compression. Both the experiments and numerical modeling confirmed the differential cell-fate transitions from the hybrid epithelial/mesenchymal state to either epithelial or mesenchymal states stochastically. Thus, we suggest that the cause of tumor heterogeneity could be its mechanical microenvironment as sensed by its cytoplasmic volume.
MIT Department
Massachusetts Institute of Technology. Department of Mechanical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.2110550118
