Single-cell RNA sequencing of proliferative stem cell population from juvenile Schistosoma mansoni worms
Ontology highlight
ABSTRACT:
ORGANISM(S): Schistosoma mansoni
PROVIDER: GSE116920 | GEO | 2018/07/12
REPOSITORIES: GEO
Similar Datasets
Project description:We generated bulk Cut&run data with antibodies agains H3K27me3 in primary mouse OPCs and OPC model cell line Oli-neu, and with antibodies agains H3K27ac in Oli-neu cell line with addition of BSA at various steps of the protocol. These datasets were used as benchmarks for the scCUT&Tag data of the mouse brain.
2021-02-10 | GSE163495 | GEO
Project description:Current methods for quantification of differences between scRNA-seq datasets collected in multiple conditions focus on discrete regions of the transcriptional state space such as clusters of cells. Here, we describe a continuous measure of the effect of a perturbation across the transcriptomic space with single cell resolution. We describe the cellular state space as manifold, use a heat filter to estimate the density of each sample over the manifold, and normalize these densities to obtain the relative likelihood of observing each cell in each of the observed conditions. We develop vertex frequency clustering to identify populations of affected cells at the appropriate level of granularity. Using these selected populations we can derive gene signatures of affected populations of cells. We demonstrate both algorithms using a combination of biological and synthetic datasets.
2020-11-14 | GSE161465 | GEO
Project description:We obtained single-cell RNA-sequencing (scRNA-seq) profiles of CD14+ monocytes isolated from human peripheral blood at 0, 3 and 6 days after M-CSF stimulation (to differentiate the cells into macrophages) across multiple donors. Integration of single-cell RNA sequencing (scRNA-seq) data from multiple experiments, laboratories, and technologies can uncover biological insights, but current methods for scRNA-seq data integration are limited by a requirement for datasets to derive from functionally similar cells. We use a novel algorithm, Scanorama, to identify and merge the shared cell types among all pairs of datasets and to accurately integrate heterogeneous scRNA-seq datasets. Scanorama is sensitive to subtle temporal changes within the same cell lineage, successfully integrating functionally similar cells across time series data of CD14+ monocytes at different stages of differentiation into macrophages. Scanorama is not only able to differentiate between completely disparate cell types but is also sensitive to subtler transcriptional changes within a cell type due to processes like stimulation.
2019-02-06 | GSE126085 | GEO
Project description:The global loss of heterochromatin during aging has been observed in eukaryotes from yeast to humans, and this has been proposed to be one of the causes of aging. However, the cause of this age-associated loss of heterochromatin has remained enigmatic. Here we show that heterochromatin markers, including histone H3K9 di-/tri-methylation and HP1, decrease with age in murine muscle stem cells (MuSCs) as a consequence of the depletion of the methyl donor SAM. We find that restoration of intracellular SAM in aged MuSCs restores heterochromatin content to youthful levels and rejuvenates age-associated features including DNA damage accumulation, increased cell death, and defective muscle regeneration. SAM is not only a methyl group donor for transmethylation but it is also an aminopropyl donor for polyamine synthesis. Excessive consumption of SAM in polyamine synthesis may reduce its availability for transmethylation. Consistent with this premise, we observe that perturbation of increased polyamine synthesis by inhibiting spermidine synthase (Srm) restores the intracellular SAM content as well as heterochromatin formation, leading to improvements in aged MuSC function and regenerative capacity. Together, our studies demonstrate a direct causal link between polyamine metabolism and epigenetic dysregulation during MuSC aging.
2023-11-17 | GSE229853 | GEO
Project description:The global loss of heterochromatin during aging has been observed in eukaryotes from yeast to humans, and this has been proposed to be one of the causes of aging. However, the cause of this age-associated loss of heterochromatin has remained enigmatic. Here we show that heterochromatin markers, including histone H3K9 di-/tri-methylation and HP1, decrease with age in murine muscle stem cells (MuSCs) as a consequence of the depletion of the methyl donor SAM. We find that restoration of intracellular SAM in aged MuSCs restores heterochromatin content to youthful levels and rejuvenates age-associated features including DNA damage accumulation, increased cell death, and defective muscle regeneration. SAM is not only a methyl group donor for transmethylation but it is also an aminopropyl donor for polyamine synthesis. Excessive consumption of SAM in polyamine synthesis may reduce its availability for transmethylation. Consistent with this premise, we observe that perturbation of increased polyamine synthesis by inhibiting spermidine synthase (Srm) restores the intracellular SAM content as well as heterochromatin formation, leading to improvements in aged MuSC function and regenerative capacity. Together, our studies demonstrate a direct causal link between polyamine metabolism and epigenetic dysregulation during MuSC aging.
2023-11-17 | GSE229851 | GEO
Project description:Schistosoma mansoni is the major causative agent of schistosomiasis in the Americas. This parasite takes advantage from host signaling molecules such as cytokines and hormones to complete its development inside the host. TNF-α is the most important cytokine involved in the inflammatory response when cercaria, the infective stage, penetrates the human skin and a severe inflammatory response is started. In this work the authors describe the complete sequence of a possible TNF-α receptor in S. mansoni and detect that the receptor is most highly expressed in cercaria among all life cycle stages. In an attempt to mimic the situation at the site of skin penetration cercariae have been mechanically transformed in vitro into schistosomula and immediately exposed to human TNF-α . Exposure of these early schistosomula to the human hormone caused a large-scale change in the expression of parasite genes. Exposure of adult worms to human TNF-α caused gene expression changes as well, although the set of parasite altered genes was entirely different from that of schistosomula. This work increases the number of known signaling pathways of the parasite, and opens new perspectives into understanding the molecular components of TNF-α response as well as possibly interfering with parasite-host interaction. A platform previously designed by our group (PMID: 17517391) was used. 300 ng of RNA from adult schistosomes treated with TNF and its control were used for the hybridization. RNA amplification and labeling kit (Agilent Technologies) were used according to manufacturer´s instructions. Each sample was separately labeled with either Cy3 or Cy5. 825 ng cRNA from each amplification were used for hybridization; self-self experiments were performed. Washing and scanning procedures were according to the manufacturer´s instructions using GenePix 4000B scanner (Molecular Devices, Sunnyvale, CA, USA). Data was extracted using Feature Extraction software (Agilent Technologies). We calculated a virtual Log2 ratio between intensities of TNF-α Treated/Control, for each gene. With these ratios, we used two different approaches for SAM statistical analyses. SAM one-class approach was used to identify genes with sustained changes in their expression levels along the entire time period of observation (1 and 24 h); SAM two-class approach was used to identify genes with transient changes in their expression levels. In both cases, genes were considered differentially expressed at q-value � 0.05. Hierarchical clustering of selected genes was generated using Spotfire Decision Site software (TIBCO Software Inc., Palo Alto, CA, USA). For a gene that was represented in the array by multiple probes, we picked a single representative probe by selecting the probe with the highest absolute value of the Log2 ratio between intensities of TNF-α Treated/Control.
2010-06-24 | E-GEOD-16261 | biostudies-arrayexpress
Project description:A key challenge in single cell RNA-sequencing (scRNA-seq) data analysis are dataset- and batch-specific differences that can obscure the biological signal of interest. While there are various tools and methods to perform data integration and correct for batch effects, their performance can vary between datasets and according to the nature of the bias. Therefore, it is important to understand how batch effects manifest in order to adjust for them in a reliable way. Here, we systematically explore batch effects in scRNA-seq data from a variety of datasets according to magnitude, cell type specificity and complexity. We developed a cell-specific mixing score (\texttt{cms}) that quantifies how well cells from multiple batches are mixed. By considering distance distributions (in a lower dimensional space), the score is able to detect local batch bias and differentiate between unbalanced batches (i.e., when one cell type is more abundant in a batch) and systematic differences between cells of the same cell type. We implemented the \texttt{cms}, as well as related metrics to detect batch effects or measure structure preservation, in the CellMixS R/Bioconductor package. We systematically compare different metrics that have been proposed to quantify batch effects or bias in scRNA-seq data using real datasets with known batch effects and synthetic data that mimic various real data scenarios. While these metrics target the same question and are used interchangeably, we find differences in inter- and intra-dataset scalability, sensitivity and in a metric's ability to handle batch effects with differentially abundant cell types. We find that cell-specific metrics outperform cell type-specific and global metrics and recommend them for both method benchmarks and batch exploration.
2021-01-31 | E-MTAB-9916 | biostudies-arrayexpress
Project description:Crosslinking mass spectrometry (CXMS) is a powerful technique to study protein structures and interactions. However, software tools for CXMS data analysis suffer from poor speed and credibility, especially at a proteome scale. Here, we introduce pLink 2, a search engine with higher speed and credibility for proteome-scale identification of crosslinked peptides. With a novel two-stage open search strategy facilitated by fragment indexing, pLink 2 is ~40 times faster than pLink 1 and 3~10 times faster than Kojak. Furthermore, four new analysis methods, using simulated datasets, synthetic datasets, 15N metabolically labeled datasets, and entrapment databases, were designed to evaluate the credibility of ten state-of-the-art search engines, this systematic evaluation showed that pLink 2 achieved the highest precision and sensitivity. Finally, four whole-cell lysate datasets, previously analysed by pLink 1 in months, were reanalysed by pLink 2 only in days, with up to 27.4% more crosslinks identified. The new search engine pLink 2 and the new evaluation methods are well positioned to become new benchmarks in the CXMS research field.
2019-07-26 | PXD012109 | Pride
Project description:Schistosoma mansoni is the major causative agent of schistosomiasis in the Americas. This parasite takes advantage from host signaling molecules such as cytokines and hormones to complete its development inside the host. TNF-α is the most important cytokine involved in the inflammatory response when cercaria, the infective stage, penetrates the human skin and a severe inflammatory response is started. In this work the authors describe the complete sequence of a possible TNF-α receptor in S. mansoni and detect that the receptor is most highly expressed in cercaria among all life cycle stages. In an attempt to mimic the situation at the site of skin penetration cercariae have been mechanically transformed in vitro into schistosomula and immediately exposed to human TNF-α . Exposure of these early schistosomula to the human hormone caused a large-scale change in the expression of parasite genes. Exposure of adult worms to human TNF-α caused gene expression changes as well, although the set of parasite altered genes was entirely different from that of schistosomula. This work increases the number of known signaling pathways of the parasite, and opens new perspectives into understanding the molecular components of TNF-α response as well as possibly interfering with parasite-host interaction. A 4 x 44k microarray platform was designed with the same probe set described by our group in a previous publication (PMID: 17517391). 230 ng of RNA from schistosomula treated with TNF and its control were used for the hybridization. RNA amplification and labeling kit (Agilent Technologies) were used according to manufacturer´s instructions. Each sample was separately labeled with either Cy3 or Cy5 and 825 ng cRNA from each amplification were used for hybridization a control sample was combined with a treated sample and hybridized. Washing and scanning procedures were according to the manufacturer´s instructions using GenePix 4000B scanner (Molecular Devices, Sunnyvale, CA, USA). Data was extracted using Feature Extraction software (Agilent Technologies). Low intensity data points were filtered out according to Feature Extraction software criteria, which essentially determine those points that are significantly below the average background signal of the array. Total intensity data from each experiment were normalized by Quantiles Normalization Method, excluding positive and negative external controls. Significance Analysis of Microarray (SAM) was used as to find differentially expressed genes. z-score transformation of normalized data was performed and SAM two class tests were applied; genes were considered as significantly differentially expressed at q-value ⤠0.05. Hierarchical clustering of selected genes was generated using Spotfire Decision Site software (TIBCO Software Inc., Palo Alto, CA, USA). For a gene that was represented in the array by multiple probes, we picked a single representative probe by selecting the probe with the highest absolute value of the Log2 ratio between intensities of TNF-α Treated/Control.
2010-06-24 | E-GEOD-16260 | biostudies-arrayexpress
Project description:With the general adoption of new approach methodologies, the omic-based technologies are of particular importance for chemical hazard characterization owning to the premise that any apical endpoint change indicative of impaired health must be underpinned by some alterations at the omic level. In this work we studied cellular response to coumarin by measuring transcriptomics experiments. The HepG2 cells were treated with 0.001 μM 2,4-D for 0, 10, 30, 360 min. Each group has 3 biological replicates.
2024-02-12 | GSE221407 | GEO