Werner, B;
Case, J;
Williams, MJ;
Chkhaidze, K;
Temko, D;
Fernández-Mateos, J;
Cresswell, GD;
... Sottoriva, A; + view all
(2020)
Measuring single cell divisions in human tissues from multi-region sequencing data.
Nature Communications
, 11
, Article 1035. 10.1038/s41467-020-14844-6.
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Abstract
Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in humans remains challenging. Here, we show that multi-sample genomic data from a single time point of normal and cancer tissues contains information on single-cell divisions. We present a new theoretical framework that, applied to whole-genome sequencing data of healthy tissue and cancer, allows inferring the mutation rate and the cell survival/death rate per division. On average, we found that cells accumulate 1.14 mutations per cell division in healthy haematopoiesis and 1.37 mutations per division in brain development. In both tissues, cell survival was maximal during early development. Analysis of 131 biopsies from 16 tumours showed 4 to 100 times increased mutation rates compared to healthy development and substantial inter-patient variation of cell survival/death rates.
| Type: | Article |
|---|---|
| Title: | Measuring single cell divisions in human tissues from multi-region sequencing data |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-020-14844-6 |
| Publisher version: | https://doi.org/10.1038/s41467-020-14844-6 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Cancer genomics, Computational models, DNA damage and repair, Evolutionary theory |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology UCL > Provost and Vice Provost Offices > UCL SLASH UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities UCL > Provost and Vice Provost Offices > UCL SLASH > Faculty of Arts and Humanities > Arts and Sciences (BASc) |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10093148 |
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