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  Replicative cellular age distributions in compartmentalised tissues

Böttcher, M. A., Werner, B., Dingli, D., & Traulsen, A. (2018). Replicative cellular age distributions in compartmentalised tissues. bioRxiv. doi:10.1101/305250.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-70EF-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-70F0-F
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Böttcher, Marvin A.1, Author              
Werner, Benjamin, Author
Dingli, David, Author
Traulsen, Arne1, Author              
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1Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              

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 Abstract: The cellular age distribution of hierarchically organized tissues can reveal important insights into the dynamics of cell differentiation and self-renewal and associated cancer risks. Here, we examine theoretically the effect of progenitor compartments with varying differentiation and self-renewal capacities on the resulting observable distributions of replicative cellular ages. We find that strongly amplifying progenitor compartments, i.e. compartments with high self-renewal capacities, substantially broaden the age distributions which become skewed towards younger cells with a long tail of few old cells. However, since mutations predominantly accumulate during cell division, a few old cells may considerably increase cancer risk. In contrast, if tissues are organised into many downstream compartments with low self-renewal capacity, the shape of the replicative cell distributions in more differentiated compartments are dominated by stem cell dynamics with little added variation. In the limiting case of a strict binary differentiation tree without self-renewal, the shape of the output distribution becomes indistinguishable from the shape of the input distribution. Our results suggest that a comparison of cellular age distributions between healthy and cancerous tissues may inform about dynamical changes within the hierarchical tissue structure, i.e. an acquired increased self-renewal capacity in certain tumours.

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Language(s): eng - English
 Dates: 2018-04-202018
 Publication Status: Published in print
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 Identifiers: DOI: 10.1101/305250
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Title: bioRxiv
Source Genre: Journal
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Publ. Info: Cold Spring Harbor Laboratory
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