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View article: Recovery of human upper airway epithelium after smoking cessation is driven by a slow-cycling stem cell population and immune surveillance
Recovery of human upper airway epithelium after smoking cessation is driven by a slow-cycling stem cell population and immune surveillance Open
SUMMARY The upper airway epithelium in humans is maintained in homeostasis by a resident population of basal stem cells. In the presence of tobacco smoke these gain mutations that significantly increase their risk of transformation to lung…
View article: Methylation dynamics in the decades preceding acute myeloid leukaemia
Methylation dynamics in the decades preceding acute myeloid leukaemia Open
DNA methylation is emerging as a highly sensitive and specific marker of cancer initiation and progression. How these cancerspecific methylation changes are established in the decades before cancer, however, remains largely unknown. Here, …
View article: Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding
Quantitative measurement of phenotype dynamics during cancer drug resistance evolution using genetic barcoding Open
Cancer treatment frequently fails due to the evolution of drug-resistant cell phenotypes driven by genetic or non-genetic changes. The origin, timing, and rate of spread of these adaptations are critical for understanding drug resistance m…
View article: Evolutionary dynamics of 1,976 lymphoid malignancies predict clinical outcome
Evolutionary dynamics of 1,976 lymphoid malignancies predict clinical outcome Open
Cancer development, progression, and response to treatment are evolutionary processes, but characterising the evolutionary dynamics at sufficient scale to be clinically-meaningful has remained challenging. Here, we develop a new methodolog…
View article: Lineage tracing in human tissues
Lineage tracing in human tissues Open
The dynamical process of cell division that underpins homeostasis in the human body cannot be directly observed in vivo , but instead is measurable from the pattern of somatic genetic or epigenetic mutations that accrue in tissues over an …
View article: Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues
Fluctuating methylation clocks for cell lineage tracing at high temporal resolution in human tissues Open
Molecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methyl…
View article: Phenotypic plasticity and genetic control in colorectal cancer evolution
Phenotypic plasticity and genetic control in colorectal cancer evolution Open
Cancer evolution is driven by natural selection acting upon phenotypic trait variation. However, the extent to which phenotypic variation within a tumour is a consequence of intra-tumour genetic heterogeneity remains undetermined. Here we …
View article: Assessment of the evolutionary consequence of putative driver mutations in colorectal cancer with spatial multiomic data
Assessment of the evolutionary consequence of putative driver mutations in colorectal cancer with spatial multiomic data Open
Cancer genomic medicine relies on targeting driver genes. However, current catalogues of cancer drivers are mostly based on indirect measurements of mutation frequencies, positions or types, rather than their effect on clonal expansions in…
View article: Reconstruction of Contemporary Human Stem Cell Dynamics with Oscillatory Molecular Clocks
Reconstruction of Contemporary Human Stem Cell Dynamics with Oscillatory Molecular Clocks Open
Molecular clocks record cellular ancestry. However, currently used clocks ‘tick too slowly’ to measure the short-timescale dynamics of cellular renewal in adult tissues. Here we develop ‘rapidly oscillating DNA methylation clocks’ where on…
View article: Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs
Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs Open
Small solid-state devices are candidates for accelerating biomedical assays/drug discovery, however their potential remains unfulfilled. Here, we demonstrate that graphene-field effect transistors (FET) can be used to successfully detect t…
View article: Crypt fusion as a homeostatic mechanism in the human colon
Crypt fusion as a homeostatic mechanism in the human colon Open
Objective The crypt population in the human intestine is dynamic: crypts can divide to produce two new daughter crypts through a process termed crypt fission, but whether this is balanced by a second process to remove crypts, as recently s…