Transcriptomic profiling of shed cells enables spatial mapping of cellular turnover in human organs
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PROVIDER: PRJNA1284376 | ENA |
REPOSITORIES: ENA
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Project description:Single-cell atlases provide valuable insights into gene expression states but lack information on cellular dynamics. Understanding cell turnover rates—the time between a cell’s birth and death—can shed light on stemness potential and susceptibility to damage. However, measuring turnover rates in human organs has been a significant challenge. In this study, we integrate transcriptomic data from both tissue and shed cells to assign turnover scores to individual cells, leveraging their expression profiles in spatially resolved expression atlases. By performing RNA sequencing on shed cells from the upper gastrointestinal tract, collected via nasogastric tubes, we infer turnover rates in the human esophagus, stomach, and small intestine. Additionally, we analyze colonic fecal washes to map turnover potential in the human large intestine. Our findings reveal a subset of short-lived, interferon-stimulated colonocytes within a distinct pro-inflammatory microenvironment. Our approach introduces a dynamic dimension to single-cell atlases, offering broad applicability across different organs and diseases.
2025-08-19 | GSE301268 | GEO
Project description:Phenotypic evolution can result from gains and losses of genes, mutations in coding sequences, or regulatory mutations affecting gene expression. While the relative importance of these mechanisms is debated, regulatory evolution is recognized as a key driver of phenotypic diversity. In this study, we applied a phylogenetic model to discretized gene expression states (active or inactive) to investigate the evolutionary turnover of organ-specific transcriptomes, which we define as instances where gene expression is activated or deactivated in a particular organ. We focus on transcriptome turnover in two male reproductive organs in 11 species of the Drosophila melanogaster species group. Using the Bayesian inference method zigzag (Thompson et al. 2020), we estimate that testes express a higher proportion of the genome (65--75% of genes, depending on the species) compared to accessory glands (46--64%), with background expression noise producing less than 1% of transcripts in both organs. We find that many conserved genes have gained or lost expression in testes and accessory glands. Our model of joint transcriptome evolution, applied to 8,660 genes conserved as single copy families in all species (singleton genes), revealed similar turnover rates but distinct evolutionary trajectories in the two organs. We estimate that the genes in our data set transition between active and inactive expression states at rates on the order of 10^-9 yr^-1. The two organs experienced accelerated transcriptome turnover on different branches of the Drosophila phylogeny. The accessory glands exhibit greater variation in turnover rates among lineages, suggesting a lower baseline rate with bursts of rapid evolution in a subset of branches on the phylogeny. We do not observe significant differences in turnover rates between X-linked and autosomal genes. Genes that encode transcription factors transition between active and inactive states slower than non-TF genes in the accessory gland, but slightly faster in the testis. The results are robust to the choice of probability cut-offs used to discretize gene expression states, and there is good agreement between the estimates of expression states from zigzag and the inferences from the phylogenetic model. Overall, our study highlights the complex dynamics of transcriptome evolution in male reproductive organs. We discuss the benefits and challenges associated with investigating the evolution of gene expression as a binary trait and suggest potentially fruitful avenues for further methodological development.
2024-10-15 | GSE274048 | GEO
Project description:Profiling of chromosomal gains and losses in a genomic complement of stem cells from human exfoliated deciduous teeth comparing control undifferentieated SHED with hepatocyte differentiated SHED.
2018-02-01 | GSE102974 | GEO
Project description:Suppression of neurons in circumventricular organs enables months-long survival without water in thirteen-lined ground squirrels
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Project description:Paired-cell sequencing enables spatial gene expression mapping of liver endothelial cells
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Project description:In spite of its central role in biology and disease, protein turnover is a largely understudied aspect of most proteomic studies due to the complexity of computational workflows that analyze in-vivo turnover rates. To address this need, we developed a new computational tool, TurnoveR, to accurately calculate protein turnover rates from mass spectrometric analysis of metabolic labeling experiments in Skyline, a free and open-source proteomics software platform. TurnoveR is a straightforward graphical interface that enables seamless integration of protein turnover analysis into a traditional proteomics workflow in Skyline, allowing users to take advantage of the advanced and flexible data visualization and curation features built into the software. The TurnoveR computational pipeline performs critical steps to determine protein turnover rates, including isotopologue demultiplexing, precursor-pool correction, statistical analysis, and generation of data reports and visualizations. This workflow is compatible with many mass spectrometric platforms and re-capitulates turnover rates and differential changes in turnover rates between treatment groups calculated in previous studies. We expect that the addition of TurnoveR to the widely used Skyline proteomics software will facilitate wider utilization of protein turnover analysis in highly relevant biological models, including aging, neurodegeneration, and skeletal muscle atrophy.
2022-02-22 | MSV000088893 | MassIVE
Project description:Measuring the properties of endogenous cell proteins, such as expression level, subcellular localization and turnover rates, on a whole proteome level remains a major challenge in the post-genome era. Quantitative methods for measuring mRNA expression do not reliably predict corresponding protein levels and provide little or no information on other protein properties. Here we describe a combined pulse-labelling, spatial proteomics and data analysis strategy to characterize the expression, localization, synthesis, degradation and turnover rates of endogenously expressed, untagged human proteins in different subcellular compartments. Using quantitative mass spectrometry and SILAC, a total of 80,098 peptides from 8,041 HeLa proteins were quantified, and their spatial distribution between the cytoplasm, nucleus and nucleolus determined and visualised using specialised software tools developed in PepTracker. Using information from ion intensities and rates of change in isotope ratios, protein abundance levels and protein synthesis, degradation and turnover rates were calculated for the whole cell and for the respective cytoplasmic, nuclear and nucleolar compartments. Expression levels of endogenous HeLa proteins varied by up to seven orders of magnitude. The average turnover rate for HeLa proteins was approximately 20 hours. Turnover rate did not correlate with either molecular weight or net charge, but did correlate with abundance, with highly abundant proteins showing longer than average half-lives. Fast turnover proteins had overall a higher frequency of PEST motifs than slow turnover proteins but no general correlation was observed between amino or carboxy terminal amino acid identities and turnover rates. A subset of proteins was identified that exist in pools with different turnover rates depending on their subcellular localization. This strongly correlated with subunits of large, multi-protein complexes, suggesting a general mechanism whereby their assembly is controlled in a different subcellular location to their main site of function.
2015-12-01 | PXD003258 | Pride
Project description:We use a metabolic labeling strategy for directly measuring nucleosome turnover to examine the effect of doxorubicin on chromatin dynamics in squamous cell carcinoma cell lines derived from genetically defined mice. We find that doxorubicin enhances nucleosome turnover around gene promoters, and turnover correlates with gene expression level. Keywords: Chromatin affinity-purification on microarray 26 CATCH-IT arrays and 8 expression arrays.
2013-04-19 | E-GEOD-43753 | biostudies-arrayexpress
Project description:We profiled hematopoietic, lymphoid and peripheral fetal organs to systematically assess the heterogeneity of immune cell populations across human tissues during development. Single-cell suspensions were obtained from fresh tissue. Cells were either DAPI-CD45+ or DAPI-CD45- FACS-isolated cells, or unsorted.
2022-05-12 | E-MTAB-11343 | biostudies-arrayexpress
Project description:We profiled hematopoietic, lymphoid and peripheral fetal organs to systematically assess the heterogeneity of antigen receptors in immune cell populations across human tissues during development. Single-cell suspensions were obtained from fresh tissue. Cells were either DAPI-CD45+ or DAPI-CD45- FACS-isolated cells, or unsorted.
2022-09-23 | E-MTAB-11388 | biostudies-arrayexpress