Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386828501> ?p ?o ?g. }
Showing items 1 to 61 of
61
with 100 items per page.
- W4386828501 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.
- W4386828501 created "2023-09-19" @default.
- W4386828501 creator A5069836964 @default.
- W4386828501 creator A5080816783 @default.
- W4386828501 creator A5082497527 @default.
- W4386828501 creator A5092894710 @default.
- W4386828501 date "2023-09-18" @default.
- W4386828501 modified "2023-09-26" @default.
- W4386828501 title "Measures of genetic diversification in somatic tissues at bulk and single cell resolution suggest sources of unknown stochasticity" @default.
- W4386828501 doi "https://doi.org/10.7554/elife.89780" @default.
- W4386828501 hasPublicationYear "2023" @default.
- W4386828501 type Work @default.
- W4386828501 citedByCount "0" @default.
- W4386828501 crossrefType "posted-content" @default.
- W4386828501 hasAuthorship W4386828501A5069836964 @default.
- W4386828501 hasAuthorship W4386828501A5080816783 @default.
- W4386828501 hasAuthorship W4386828501A5082497527 @default.
- W4386828501 hasAuthorship W4386828501A5092894710 @default.
- W4386828501 hasBestOaLocation W43868285011 @default.
- W4386828501 hasConcept C104317684 @default.
- W4386828501 hasConcept C134305767 @default.
- W4386828501 hasConcept C144024400 @default.
- W4386828501 hasConcept C1491633281 @default.
- W4386828501 hasConcept C149923435 @default.
- W4386828501 hasConcept C180754005 @default.
- W4386828501 hasConcept C2776950831 @default.
- W4386828501 hasConcept C28328180 @default.
- W4386828501 hasConcept C2908647359 @default.
- W4386828501 hasConcept C501734568 @default.
- W4386828501 hasConcept C54355233 @default.
- W4386828501 hasConcept C86803240 @default.
- W4386828501 hasConcept C98638677 @default.
- W4386828501 hasConceptScore W4386828501C104317684 @default.
- W4386828501 hasConceptScore W4386828501C134305767 @default.
- W4386828501 hasConceptScore W4386828501C144024400 @default.
- W4386828501 hasConceptScore W4386828501C1491633281 @default.
- W4386828501 hasConceptScore W4386828501C149923435 @default.
- W4386828501 hasConceptScore W4386828501C180754005 @default.
- W4386828501 hasConceptScore W4386828501C2776950831 @default.
- W4386828501 hasConceptScore W4386828501C28328180 @default.
- W4386828501 hasConceptScore W4386828501C2908647359 @default.
- W4386828501 hasConceptScore W4386828501C501734568 @default.
- W4386828501 hasConceptScore W4386828501C54355233 @default.
- W4386828501 hasConceptScore W4386828501C86803240 @default.
- W4386828501 hasConceptScore W4386828501C98638677 @default.
- W4386828501 hasLocation W43868285011 @default.
- W4386828501 hasOpenAccess W4386828501 @default.
- W4386828501 hasPrimaryLocation W43868285011 @default.
- W4386828501 hasRelatedWork W1975253683 @default.
- W4386828501 hasRelatedWork W2057739827 @default.
- W4386828501 hasRelatedWork W2070922469 @default.
- W4386828501 hasRelatedWork W2097772261 @default.
- W4386828501 hasRelatedWork W2132042562 @default.
- W4386828501 hasRelatedWork W2149943693 @default.
- W4386828501 hasRelatedWork W2223919059 @default.
- W4386828501 hasRelatedWork W2558911725 @default.
- W4386828501 hasRelatedWork W2607209303 @default.
- W4386828501 hasRelatedWork W2613868166 @default.
- W4386828501 isParatext "false" @default.
- W4386828501 isRetracted "false" @default.
- W4386828501 workType "article" @default.