Heritable tumor cell division rate heterogeneity induces clonal dominance.
Tumors consist of a hierarchical population of cells that differ in their phenotype and genotype. This hierarchical organization of cells means that a few clones (i.e., cells and several generations of offspring) are abundant while most are rare, which is called clonal dominance. Such dominance also...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-02-01
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| Series: | PLoS Computational Biology |
| Online Access: | http://europepmc.org/articles/PMC5825147?pdf=render |
| _version_ | 1828864331534565376 |
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| author | Margriet M Palm Marjet Elemans Joost B Beltman |
| author_facet | Margriet M Palm Marjet Elemans Joost B Beltman |
| author_sort | Margriet M Palm |
| collection | DOAJ |
| description | Tumors consist of a hierarchical population of cells that differ in their phenotype and genotype. This hierarchical organization of cells means that a few clones (i.e., cells and several generations of offspring) are abundant while most are rare, which is called clonal dominance. Such dominance also occurred in published in vitro iterated growth and passage experiments with tumor cells in which genetic barcodes were used for lineage tracing. A potential source for such heterogeneity is that dominant clones derive from cancer stem cells with an unlimited self-renewal capacity. Furthermore, ongoing evolution and selection within the growing population may also induce clonal dominance. To understand how clonal dominance developed in the iterated growth and passage experiments, we built a computational model that accurately simulates these experiments. The model simulations reproduced the clonal dominance that developed in in vitro iterated growth and passage experiments when the division rates vary between cells, due to a combination of initial variation and of ongoing mutational processes. In contrast, the experimental results can neither be reproduced with a model that considers random growth and passage, nor with a model based on cancer stem cells. Altogether, our model suggests that in vitro clonal dominance develops due to selection of fast-dividing clones. |
| first_indexed | 2024-12-13T04:03:31Z |
| format | Article |
| id | doaj.art-dd648e88c26c416ba1d89756a7664d38 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-13T04:03:31Z |
| publishDate | 2018-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-dd648e88c26c416ba1d89756a7664d382022-12-22T00:00:21ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582018-02-01142e100595410.1371/journal.pcbi.1005954Heritable tumor cell division rate heterogeneity induces clonal dominance.Margriet M PalmMarjet ElemansJoost B BeltmanTumors consist of a hierarchical population of cells that differ in their phenotype and genotype. This hierarchical organization of cells means that a few clones (i.e., cells and several generations of offspring) are abundant while most are rare, which is called clonal dominance. Such dominance also occurred in published in vitro iterated growth and passage experiments with tumor cells in which genetic barcodes were used for lineage tracing. A potential source for such heterogeneity is that dominant clones derive from cancer stem cells with an unlimited self-renewal capacity. Furthermore, ongoing evolution and selection within the growing population may also induce clonal dominance. To understand how clonal dominance developed in the iterated growth and passage experiments, we built a computational model that accurately simulates these experiments. The model simulations reproduced the clonal dominance that developed in in vitro iterated growth and passage experiments when the division rates vary between cells, due to a combination of initial variation and of ongoing mutational processes. In contrast, the experimental results can neither be reproduced with a model that considers random growth and passage, nor with a model based on cancer stem cells. Altogether, our model suggests that in vitro clonal dominance develops due to selection of fast-dividing clones.http://europepmc.org/articles/PMC5825147?pdf=render |
| spellingShingle | Margriet M Palm Marjet Elemans Joost B Beltman Heritable tumor cell division rate heterogeneity induces clonal dominance. PLoS Computational Biology |
| title | Heritable tumor cell division rate heterogeneity induces clonal dominance. |
| title_full | Heritable tumor cell division rate heterogeneity induces clonal dominance. |
| title_fullStr | Heritable tumor cell division rate heterogeneity induces clonal dominance. |
| title_full_unstemmed | Heritable tumor cell division rate heterogeneity induces clonal dominance. |
| title_short | Heritable tumor cell division rate heterogeneity induces clonal dominance. |
| title_sort | heritable tumor cell division rate heterogeneity induces clonal dominance |
| url | http://europepmc.org/articles/PMC5825147?pdf=render |
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