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...

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Bibliographic Details
Published in:PLoS computational biology Vol. 14; no. 2; p. e1005954
Main Authors: Palm, Margriet M., Elemans, Marjet, Beltman, Joost B.
Format: Journal Article
Language:English
Published: United States Public Library of Science 01.02.2018
Public Library of Science (PLoS)
Subjects:
Autosomal dominant inheritance
Bar codes
Bioinformatics
Biology and Life Sciences
Cancer
Cell division
Cell self-renewal
Computer applications
Computer simulation
Dominance
Epigenetics
Experiments
Gene expression
Genetic aspects
Genotypes
Health aspects
Heterogeneity
Labeling
Medicine and Health Sciences
Mutation
Offspring
Phenotypes
Physiological aspects
R&D
Research & development
Research and Analysis Methods
Software
Stem cells
Tumor cells
Tumors
Netherlands
ISSN:1553-7358, 1553-734X, 1553-7358
Online Access:Get full text
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Summary: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.
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The authors have declared that no competing interests exist.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1005954