Volumetric compression develops noise-driven single-cell heterogeneity
<jats:title>Significance</jats:title> <jats:p>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 fro...
| Main Authors: | , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Proceedings of the National Academy of Sciences
2023
|
| Online Access: | https://hdl.handle.net/1721.1/152549 |
| _version_ | 1826194155883200512 |
|---|---|
| author | Zhao, Xing Hu, Jiliang Li, Yiwei Guo, Ming |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Zhao, Xing Hu, Jiliang Li, Yiwei Guo, Ming |
| author_sort | Zhao, Xing |
| collection | MIT |
| description | <jats:title>Significance</jats:title>
<jats:p>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.</jats:p> |
| first_indexed | 2024-09-23T09:51:47Z |
| format | Article |
| id | mit-1721.1/152549 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:51:47Z |
| publishDate | 2023 |
| publisher | Proceedings of the National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/1525492024-01-22T21:50:57Z Volumetric compression develops noise-driven single-cell heterogeneity Zhao, Xing Hu, Jiliang Li, Yiwei Guo, Ming Massachusetts Institute of Technology. Department of Mechanical Engineering <jats:title>Significance</jats:title> <jats:p>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.</jats:p> 2023-10-30T18:29:59Z 2023-10-30T18:29:59Z 2021-12-21 2023-10-30T18:22:52Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/152549 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). en 10.1073/pnas.2110550118 Proceedings of the National Academy of Sciences 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. application/pdf Proceedings of the National Academy of Sciences Proceedings of the National Academy of Sciences |
| spellingShingle | Zhao, Xing Hu, Jiliang Li, Yiwei Guo, Ming Volumetric compression develops noise-driven single-cell heterogeneity |
| title | Volumetric compression develops noise-driven single-cell heterogeneity |
| title_full | Volumetric compression develops noise-driven single-cell heterogeneity |
| title_fullStr | Volumetric compression develops noise-driven single-cell heterogeneity |
| title_full_unstemmed | Volumetric compression develops noise-driven single-cell heterogeneity |
| title_short | Volumetric compression develops noise-driven single-cell heterogeneity |
| title_sort | volumetric compression develops noise driven single cell heterogeneity |
| url | https://hdl.handle.net/1721.1/152549 |
| work_keys_str_mv | AT zhaoxing volumetriccompressiondevelopsnoisedrivensinglecellheterogeneity AT hujiliang volumetriccompressiondevelopsnoisedrivensinglecellheterogeneity AT liyiwei volumetriccompressiondevelopsnoisedrivensinglecellheterogeneity AT guoming volumetriccompressiondevelopsnoisedrivensinglecellheterogeneity |