Single-cell functional pharmacogenomics reveal cell decision information within gene expression noise
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA577469 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10276247.fastq.gz | Fastqsanger.gz | |||
| SRR10276248.fastq.gz | Fastqsanger.gz | |||
| SRR10276249.fastq.gz | Fastqsanger.gz | |||
| SRR10276250.fastq.gz | Fastqsanger.gz | |||
| SRR10276251.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 19 |
Similar Datasets
Project description:Single HeLa cells were treated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, 25ng/ml, 50min) to determine their response profiles (“high” or “low”) by live-cell microscopy using a FRET sensor of capase-8 dynamics, a predictor of “cell death” or “cell survival”, respectively. Based on their response profile, cells were isolated by laser-capture microdissection and analyzed by single-cell RNA sequencing to determine the gene expression signature associated with their drug response profile.
2020-09-23 | GSE138832 | GEO
Project description:Fuzziness and noise in nucleosomal architecture
| PRJEB4709 | ENA
Project description:This project has been completed and consisted of a randomised trial of six tailored decision aids giving patients evidence-based information about faecal occult blood test screening for bowel cancer. 314 Australians aged between 50-74 years were recruited from five general practices and randomised to received either the tailored decision aid with age-gender and family history specific information and values clarification exercise or a standard government information sheet.
The decision aid significantly increased the proportion of people who were informed participants in the screening program.
| 2015614 | ecrin-mdr-crc
Project description:Environmental stressors present in the modern world can have a fundamental effect on the physiology and health of humans. Exposure to stressors like air pollution, heat and traffic noise has been linked to a pronounced increase in non-communicable diseases. Specifically, aircraft noise has been identified as a risk factor for cardiovascular and metabolic diseases, such as arteriosclerosis, heart failure, stroke and diabetes. Noise stress leads to neuronal activation with subsequent stress hormone release that ultimately leads to activation of the renin-angiotensin-aldosterone system, increasing inflammation and oxidative stress, with dramatic effects on the cardiovascular system. However, despite the epidemiological evidence of a link between noise stress and metabolic dysfunction, the consequences of exposure at the molecular, metabolic level of the cardiovascular system are largely unknown. Here we use a murine model system of aircraft noise exposure to show that noise stress profoundly alters heart metabolism. Within days of exposing animals to aircraft noise the heart has a reduced potential for utilising fatty-acid beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain for generating ATP. This is compensated by shifting energy production towards glycolysis. Intriguingly, the metabolic shift is reminiscent of what is observed in failing and ischaemic hearts. Our results demonstrate that within a relatively short exposure time, the cardiovascular system undergoes a fundamental metabolic shift that bears the hallmarks of cardiovascular disease. Overall, aircraft noise induces rapid, detrimental metabolic shifts in the heart, resembling patterns seen in cardiovascular diseases. These findings underscore the urgent need to comprehend molecular consequences of environmental stressors, paving the way for targeted interventions aiming mitigating health risks associated with chronic noise exposure in our modern, noisy environments.
2025-05-14 | PXD051406 | Pride
Project description:Pharmacogenomics of Statin Therapy (POST)
| PRJNA1093552 | ENA
Project description:Pharmacogenomics of Statin Therapy (POST)
| PRJNA1093553 | ENA
Project description:Pharmacogenomics of Rheumatoid Arthritis Therapy
| PRJNA294477 | ENA
Project description:Noise-induced hidden hearing loss (HHL) is a new type of hearing loss that has been identified in recent years and leads to insidious damage to the cochlea, unlike the well-known noise-induced hearing loss (NIHL). However, the cellular and molecular basis for it remains to be elucidated. Here, we established a single-cell transcriptome profile of the C57BL/6J mouse cochlea, in which we describe the transcriptome changes of individual cell types within the cochlea with HHL and NIHL. Mice in the HHL group were exposed to 110 dB of noise for 2 hours, and those in the NIHL group were exposed to 115 dB of noise for 4 hours for 3 days. The cochlea was taken 6 hours after the last noise exposure. The control group was not exposed to noise, with other conditions being the same as those in the noise-exposed group. The results of sequencing at the single-cell level help us gain a deeper understanding of the mechanisms of the development of HHL and NIHL.
2024-06-24 | GSE252285 | GEO
Project description:The molecular mechanisms underlying the great differences in susceptibility to noise-induced hearing loss (NIHL) exhibited by both humans and laboratory animals are unknown. Using microarray technology, the present study demonstrates that the effects of noise overexposure on the expression of molecules likely to be important to the development of NIHL differ among inbred mice that have distinctive susceptibilities to NIHL including B6.CAST, 129X1/SvJ, and 129S1/SvImJ. The noise-exposure protocol produced, on average, a permanent loss of about 40 dB in sensitivity for auditory brainstem responses in susceptible B6.CAST mice, but no threshold elevations for the two resistant 129S1/SvImJ and 129X1/SvJ substrains. Measurements of noise-induced gene expression changes 6 h after the noise exposure revealed significant alterations in the expression levels of 48 genes in the resistant mice, while by these same criteria, there were seven differentially expressed genes in the susceptible B6.CAST mice. Differentially expressed genes in both groups of mice included subsets of transcription factors. However, only in the resistant mice was there a significant induction of proteins involved in cell-survival pathways such as HSP70, HSP40, p21, GADD45ï¢, Ier3, and Nfï«ï¢iïº. Moreover, increased expression of three of these factors after noise was confirmed at the protein level. Drastically enhanced HSP70, GADD45ï¢, and p21 immunostaining were detected 6 h after the noise exposure in subsets of cells of the lateral wall, spiral limbus, and organ of Corti as well as in cochlear nerve fibers. Upregulation of these proteins after noise exposure likely contributes to the prevalence of survival cellular pathways and thus to the resistance to NIHL that is characteristic of the 129X1/SvJ mice. Experiment Overall Design: Female 10-wk-old mice of the B6.CAST and 129X1/SvJ strains were divided randomly into non-noise control and noise-exposure groups. The non-noise mice served as controls in the gene-profiling experiments to control for the stress induced by experimenter handling and/or confinement of the mice in the noise-exposure chamber that was not directly related to the noise. This mice were in the noise chamber for a sham exposure. In contrast, the ânoiseâ groups were exposed to a 105-dB SPL, 10-kHz octave band of noise for 1 h and sacrificed 6 h after the exposure. Of each of these major groups, eight mice were used for each of three 129X1/SvJ control and three noise-exposed 129X1/SvJ arrays and two B6.CAST control and two noise-exposed B6.CAST arrays. Consequently within each subgroup the arrays are biological replicates.
2008-10-25 | E-GEOD-8342 | biostudies-arrayexpress
Project description:Phenotypic cell-to-cell variability within clonal populations may be amanifestation of "gene expression noise", or it may reflect stablephenotypic variants. Such "non-genetic cell individuality" can arisefrom the slow fluctuations of protein levels in mammalian cells. Thesefluctuations produce persistent cell individuality, thereby rendering aclonal population heterogeneous. However, it remains unknown whetherthis heterogeneity may account for the stochasticity of cell fatedecisions in stem cells which depends on the kinetics that underliesheterogeneity. Here we show that in clonal populations of hematopoieticprogenitor cells, spontaneous "outlier" cells with extremely high or lowexpression levels of the stem cell marker Sca-1 reconstitute theparental distribution of Sca-1 but do so only after more than one week.This slow relaxation is described by a Gaussian-Mixture Model (GMM) thatincorporates noise-driven transitions between discrete subpopulations,suggesting hidden multi-stability within one cell type. Despiteclonality, the Sca-1 outliers had distinct transcriptomes. Although theunique gene expression profiles eventually reversed to that of themedian cells, they lasted long enough to confer a greatly differentproclivity for choosing either the erythroid or myeloid lineages. Preference in lineage choice was associated with elevated expression oflineage-specific transcription factors, such as > 200-fold increase inGATA1 among the erythroid-prone cells, or > 15-fold PU.1 expressionamong myeloid-prone cell. Thus, clonal heterogeneity of gene expressionlevel is not due to independent noise in the expression of individualgenes, but reflects metastable states of a slowly fluctuatingtranscriptome that is distinct in individual cells and may govern thereversible, stochastic priming of multipotent progenitor cells in cellfate decision. Keywords: murine EML cell line In the study presented here, the highest, middle, and lowest 15% Sca-1expressors from a clonal population of EML cells were used to acquireexpression profiles of a total of 46,628 unique genes using the IlluminaMouse-6 v1.1 microbead chips. Here, the Rank-Invariant normalized datais provided along with the individual raw data files.
2008-05-22 | E-GEOD-10772 | biostudies-arrayexpress