Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386828311> ?p ?o ?g. }
Showing items 1 to 53 of
53
with 100 items per page.
- W4386828311 abstract "Intra-tissue genetic heterogeneity is universal to both healthy and cancerous tissues. It emerges from the stochastic accumulation of somatic mutations throughout development and homeostasis. By combining population genetics theory and genomic information, genetic heterogeneity can be exploited to infer tissue organisation and dynamics in vivo. However, many basic quantities, for example the dynamics of tissue specific stem cells remain difficult to quantify precisely. Here we show that single cell and bulk sequencing data inform on different aspects of the underlying stochastic processes. Bulk derived variant allele frequency spectra (VAF) show transitions from growing to constant stem cell populations with age in samples of healthy oesophagus epithelium. Single-cell mutational burden distributions allow a sample size independent measure of mutation and proliferation rates. Mutation rates in adult haematopietic stem cells are higher compared to inferences during development, suggesting additional proliferation independent effects. Furthermore, single cell derived VAF spectra contain information on the number of tissue specific stem cells. In haematopiesis, we find approximately 2 × 105 HSCs, if all stem cells divide symmetrically. However, the single cell mutational burden distribution is over-dispersed compared to a model of Poisson distributed random mutations suggesting currently unknown processes induce additional stochasticity. Possible candidates for these processes may be occasional bursts of stem cell divisions, potentially in response to injury, or non-constant mutation rates either through environmental exposures or cell intrinsic variation." @default.
- W4386828311 created "2023-09-19" @default.
- W4386828311 date "2023-09-18" @default.
- W4386828311 modified "2023-10-01" @default.
- W4386828311 title "Reviewer #1 (Public Review): Measures of genetic diversification in somatic tissues at bulk and single cell resolution suggest sources of unknown stochasticity" @default.
- W4386828311 doi "https://doi.org/10.7554/elife.89780.1.sa1" @default.
- W4386828311 hasPublicationYear "2023" @default.
- W4386828311 type Work @default.
- W4386828311 citedByCount "0" @default.
- W4386828311 crossrefType "peer-review" @default.
- W4386828311 hasBestOaLocation W43868283111 @default.
- W4386828311 hasConcept C104317684 @default.
- W4386828311 hasConcept C134305767 @default.
- W4386828311 hasConcept C144024400 @default.
- W4386828311 hasConcept C1491633281 @default.
- W4386828311 hasConcept C149923435 @default.
- W4386828311 hasConcept C180754005 @default.
- W4386828311 hasConcept C2776950831 @default.
- W4386828311 hasConcept C28328180 @default.
- W4386828311 hasConcept C2908647359 @default.
- W4386828311 hasConcept C501734568 @default.
- W4386828311 hasConcept C54355233 @default.
- W4386828311 hasConcept C86803240 @default.
- W4386828311 hasConcept C98638677 @default.
- W4386828311 hasConceptScore W4386828311C104317684 @default.
- W4386828311 hasConceptScore W4386828311C134305767 @default.
- W4386828311 hasConceptScore W4386828311C144024400 @default.
- W4386828311 hasConceptScore W4386828311C1491633281 @default.
- W4386828311 hasConceptScore W4386828311C149923435 @default.
- W4386828311 hasConceptScore W4386828311C180754005 @default.
- W4386828311 hasConceptScore W4386828311C2776950831 @default.
- W4386828311 hasConceptScore W4386828311C28328180 @default.
- W4386828311 hasConceptScore W4386828311C2908647359 @default.
- W4386828311 hasConceptScore W4386828311C501734568 @default.
- W4386828311 hasConceptScore W4386828311C54355233 @default.
- W4386828311 hasConceptScore W4386828311C86803240 @default.
- W4386828311 hasConceptScore W4386828311C98638677 @default.
- W4386828311 hasLocation W43868283111 @default.
- W4386828311 hasOpenAccess W4386828311 @default.
- W4386828311 hasPrimaryLocation W43868283111 @default.
- W4386828311 hasRelatedWork W1975253683 @default.
- W4386828311 hasRelatedWork W2057739827 @default.
- W4386828311 hasRelatedWork W2070922469 @default.
- W4386828311 hasRelatedWork W2097772261 @default.
- W4386828311 hasRelatedWork W2132042562 @default.
- W4386828311 hasRelatedWork W2149943693 @default.
- W4386828311 hasRelatedWork W2223919059 @default.
- W4386828311 hasRelatedWork W2558911725 @default.
- W4386828311 hasRelatedWork W2607209303 @default.
- W4386828311 hasRelatedWork W2613868166 @default.
- W4386828311 isParatext "false" @default.
- W4386828311 isRetracted "false" @default.
- W4386828311 workType "peer-review" @default.