Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells
Phenotypic heterogeneity is a hallmark of aggressive cancer behaviour and a clinical challenge. Despite much characterisation of this heterogeneity at a multi-omics level in many cancers, we have a limited understanding of how this heterogeneity emerges spontaneously in an isogenic cell population....
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/3/348 |
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| author | Paras Jain Sugandha Bhatia Erik W. Thompson Mohit Kumar Jolly |
| author_facet | Paras Jain Sugandha Bhatia Erik W. Thompson Mohit Kumar Jolly |
| author_sort | Paras Jain |
| collection | DOAJ |
| description | Phenotypic heterogeneity is a hallmark of aggressive cancer behaviour and a clinical challenge. Despite much characterisation of this heterogeneity at a multi-omics level in many cancers, we have a limited understanding of how this heterogeneity emerges spontaneously in an isogenic cell population. Some longitudinal observations of dynamics in epithelial-mesenchymal heterogeneity, a canonical example of phenotypic heterogeneity, have offered us opportunities to quantify the rates of phenotypic switching that may drive such heterogeneity. Here, we offer a mathematical modeling framework that explains the salient features of population dynamics noted in PMC42-LA cells: (a) predominance of EpCAM<sup>high</sup> subpopulation, (b) re-establishment of parental distributions from the EpCAM<sup>high</sup> and EpCAM<sup>low</sup> subpopulations, and (c) enhanced heterogeneity in clonal populations established from individual cells. Our framework proposes that fluctuations or noise in content duplication and partitioning of SNAIL—an EMT-inducing transcription factor—during cell division can explain spontaneous phenotypic switching and consequent dynamic heterogeneity in PMC42-LA cells observed experimentally at both single-cell and bulk level analysis. Together, we propose that asymmetric cell division can be a potential mechanism for phenotypic heterogeneity. |
| first_indexed | 2024-03-09T20:04:36Z |
| format | Article |
| id | doaj.art-2c148ea42b6c4de787b87f18d5810052 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T20:04:36Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-2c148ea42b6c4de787b87f18d58100522023-11-24T00:34:36ZengMDPI AGBiomolecules2218-273X2022-02-0112334810.3390/biom12030348Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer CellsParas Jain0Sugandha Bhatia1Erik W. Thompson2Mohit Kumar Jolly3Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, IndiaSchool of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4000, AustraliaSchool of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane 4000, AustraliaCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, IndiaPhenotypic heterogeneity is a hallmark of aggressive cancer behaviour and a clinical challenge. Despite much characterisation of this heterogeneity at a multi-omics level in many cancers, we have a limited understanding of how this heterogeneity emerges spontaneously in an isogenic cell population. Some longitudinal observations of dynamics in epithelial-mesenchymal heterogeneity, a canonical example of phenotypic heterogeneity, have offered us opportunities to quantify the rates of phenotypic switching that may drive such heterogeneity. Here, we offer a mathematical modeling framework that explains the salient features of population dynamics noted in PMC42-LA cells: (a) predominance of EpCAM<sup>high</sup> subpopulation, (b) re-establishment of parental distributions from the EpCAM<sup>high</sup> and EpCAM<sup>low</sup> subpopulations, and (c) enhanced heterogeneity in clonal populations established from individual cells. Our framework proposes that fluctuations or noise in content duplication and partitioning of SNAIL—an EMT-inducing transcription factor—during cell division can explain spontaneous phenotypic switching and consequent dynamic heterogeneity in PMC42-LA cells observed experimentally at both single-cell and bulk level analysis. Together, we propose that asymmetric cell division can be a potential mechanism for phenotypic heterogeneity.https://www.mdpi.com/2218-273X/12/3/348asymmetric cell divisionepithelial-mesenchymal heterogeneityepithelial-mesenchymal plasticitypopulation dynamics |
| spellingShingle | Paras Jain Sugandha Bhatia Erik W. Thompson Mohit Kumar Jolly Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells Biomolecules asymmetric cell division epithelial-mesenchymal heterogeneity epithelial-mesenchymal plasticity population dynamics |
| title | Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells |
| title_full | Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells |
| title_fullStr | Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells |
| title_full_unstemmed | Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells |
| title_short | Population Dynamics of Epithelial-Mesenchymal Heterogeneity in Cancer Cells |
| title_sort | population dynamics of epithelial mesenchymal heterogeneity in cancer cells |
| topic | asymmetric cell division epithelial-mesenchymal heterogeneity epithelial-mesenchymal plasticity population dynamics |
| url | https://www.mdpi.com/2218-273X/12/3/348 |
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