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  Replicative cellular age distributions in compartmentalized tissues

Böttcher, M. A., Dingli, D., Werner, B., & Traulsen, A. (2018). Replicative cellular age distributions in compartmentalized tissues. Interface: Journal of the Royal Society, 15(145): 20180272. doi:10.1098/rsif.2018.0272.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-6724-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-6725-1
Genre: Journal Article

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Böttcher, Marvin A.1, Author              
Dingli, David, Author
Werner, Benjamin1, Author
Traulsen, A.1, Author              
Affiliations:
1Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              

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Free keywords: Compartment model, Hierarchical tissues, Mathematical models, Replicative ageing, Telomere loss, Tissue ageing, Binary trees, Chromosomes, Cytology, Histology, Mathematical models, Stem cells, Cancerous tissues, Cell differentiation, Compartment model, Healthy individuals, Input distributions, Output distribution, Replicative ageing, Telomeres, Tissue
 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 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. For several of these strongly amplifying compartments, the age distribution becomes virtually independent of the influx from the stem cell compartment. By contrast, if tissues are organized into many downstream compartments with low self-renewal capacity, the shape of the replicative cell distribution in more differentiated compartments is 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 that 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. Furthermore, we compare our theoretical results to telomere length distributions in granulocyte populations of 10 healthy individuals across different ages, highlighting that our theoretical expectations agree with experimental observations. © 2018 The Authors.

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Language(s): eng - English
 Dates: 2018-04-202018-08-072018-08-292018
 Publication Status: Published in print
 Pages: -
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 Rev. Method: -
 Identifiers: DOI: 10.1098/rsif.2018.0272
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Title: Interface : Journal of the Royal Society
  Other : J. R. Soc. Interface
Source Genre: Journal
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Publ. Info: London : Royal Society
Pages: - Volume / Issue: 15 (145) Sequence Number: 20180272 Start / End Page: - Identifier: ISSN: 1742-5689
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000018840_1