Jain, P and Bhatia, S and Thompson, EW and Jolly, MK (2022) Population Dynamics of Epithelial�Mesenchymal Heterogeneity in Cancer Cells. In: Biomolecules, 12 (3).
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Abstract
Phenotypic heterogeneity is a hallmark of aggressive cancer behaviour and a clinical chal-lenge. 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 heteroge-neity, 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 EpCAMhigh subpopulation, (b) re�establishment of parental distributions from the EpCAMhigh and EpCAMlow 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
| Item Type: | Journal Article |
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| Publication: | Biomolecules |
| Publisher: | MDPI |
| Additional Information: | The copyright for this article belongs to Authors |
| Keywords: | epithelial cell adhesion molecule; transcription factor Snail, Article; cancer cell; cell division; cell population; epithelial mesenchymal transition; epithelium cell; mathematical model; nonhuman; phenotype; population dynamics; population growth |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering |
| Date Deposited: | 21 Mar 2022 07:37 |
| Last Modified: | 21 Mar 2022 07:37 |
| URI: | http://eprints.iisc.ac.in/id/eprint/71574 |
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