We obtained radiographically-localized biopsies during glioma resection surgeries to sample the tumor core and margins from multiple glioma patients. We also procured fresh, non-neoplastic brain tissue specimens from multiple patients having procedures to relieve epilespy symptoms or to place shunts to treat normal pressure hydrocephalus. We then used RNA-Seq to compare expression patterns between geographically distinct regions of gliomas and computational deconvolution to estimate cell type-specific expression patterns in different disease subtypes. Overall design: RNA-Seq analysis in 39 contrast-enhancing glioma core samples, 36 non-enhancing FLAIR glioma margin samples, and 17 non-neoplastic brain tissue samples.
MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.
No sample metadata fields
View SamplesNon-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo. Overall design: Single-cell RNA sequencing (SMARTSeq2) of 373 human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets.
Subject, Time
View SamplesNon-typhoidal Salmonella (NTS) are among of the most important food-borne pathogens. Recently, a highly invasive multi-drug resistant S. Typhimurium of a distinct multilocus sequence type (MLST), ST313, has emerged across sub-Saharan Africa as a major cause of lethal bacteraemia in children and immunosuppressed adults. Encounters between dendritic cells (DCs) and invading bacteria determine the course of infection but whether or how ST313 might usurp DC mediated defence has not been reported. Here we utilised fluorescently labelled invasive and non-invasive strains of Salmonella combined with single-cell RNA sequencing to study the transcriptomes of individual infected and bystander DCs. The transcriptomes displayed a repertoire of cell instrinsic and extrinsic innate response states that differed between invasive and non-invasive strains. Gene expression heterogeneity was increased in DCs challenged with invasive Salmonella. DCs exposed but not harbouring invasive Salmonella exhibited a hyper-activated profile that likely facilitates trafficking of infected cells and dissemination of internalised intact bacteria. In contrast, invasive Salmonella containing DCs demonstrate reprogramming of trafficking genes required to avoid autophagic destruction. Furthermore, these cells displayed differential expression of tolerogenic IL10 and MARCH1 enabling CD83 mediated adaptive immune evasion. Altogether our data illustrate pathogen cell-to cell variability directed by a Salmonella invasive strain highlighting potential mechanisms of host adaption with implications for dissemination in vivo. Overall design: RNA-seq of mini-bulks (5000 cells) of human monocyte derived dendritic cells infected with S. Typhimurium strain LT2 or D23580 or left uninfected
Invasive Salmonella exploits divergent immune evasion strategies in infected and bystander dendritic cell subsets.
Subject, Time
View SamplesThe role of diet in the prevention of breast cancer is widely accepted, yet little is known on how early dietary effects mitigate adult cancer risk. Soy consumption is associated with reduced breast cancer risk in women, an effect largely attributed to the soy isoflavone genistein (GEN). We previously showed lower chemically-induced mammary tumor incidence in young adult rats with lifetime dietary intake of soy protein isolate (SPI), a highly refined soy product in infant formula, than in those fed the control diet Casein (CAS). To gain insight into signaling pathways underlying dietary tumor protection, we performed genome-wide expression profiling of mammary epithelial cells from young adult rats lifetime fed CAS, SPI, or supplemental GEN-based diets. We identified mammary epithelial genes regulated by SPI (79 total) and GEN (99 total) using Affymetrix rat 230A GeneChip arrays and found minimal overlap in gene expression patterns. We showed that the regulated transcripts functionally cluster in biochemical pathways involving metabolism, immune response, signal transduction, and ion transport. We confirmed the differential expression of Wnt (Wnt5a, Sfrp2) and Notch (Notch2, Hes1) signaling components by SPI and/or GEN using QPCR. Wnt pathway inhibition by GEN was supported by lower Cyclin D1 immunoreactivity in mammary ductal epithelium of GEN relative to CAS and SPI, despite their comparable levels of membrane-localized E-cadherin and -catenin. Identification of distinct GEN and SPI responsive genes in mammary epithelial cells may define early events contributing to tumor protection by diet relevant to the prevention of breast and other types of cancer.
Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors.
No sample metadata fields
View SamplesOptically decodable beads link the identity of an analyte or sample to a measurement through an optical barcode, enabling libraries of biomolecules to be captured on beads in solution and decoded by fluorescence. This approach has been foundational to microarray, sequencing, and flow-based expression profiling technologies. We have combined microfluidics with optically decodable beads to link phenotypic analysis of living cells to sequencing. As a proof-of-concept, we applied this to demonstrate an accurate and scalable tool for connecting live cell imaging to single-cell RNA-Seq called Single Cell Optical Phenotyping and Expression (SCOPE-Seq). Overall design: Performed SCOPE-Seq on thousands of cells from two cell lines.
SCOPE-Seq: a scalable technology for linking live cell imaging and single-cell RNA sequencing.
No sample metadata fields
View SamplesA Krppel-like factor 9 (Klf9) regulated network in HEC-1-A endometrial carcinoma cells encompassing adhesion proteins, steroid- and menstrual cycle-regulated proteins of the uterine endometrium, novel membrane proteins, and nuclear receptors
The Krüppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression.
No sample metadata fields
View SamplesThis study is part of a larger multidisciplinary study entitled A dormant sub-population expressing interleukin-1 receptor characterises anti-estrogen resistant ALDH+ breast cancer stem cells.
Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH<sup>+</sup> Breast Cancer Stem Cells.
Specimen part, Disease, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival.
Specimen part
View SamplesThe aim of this study is to address the functional role of miRNAs in the FoxD1+ renal stroma progenitors and derivatives during embryonic kidney development. To achieve this, we generated transgenic mice that lack miRNAs in the renal stroma lineage (FoxD1 Cre;Dicer), and performed a microarray analysis on E15.5 whole kidneys to determine the transcriptional changes.
Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival.
Specimen part
View SamplesThe aim of this study is to address the functional role of miRNAs in the FoxD1+ renal stroma progenitors and derivatives during embryonic kidney development. To achieve this, we generated transgenic mice that lack miRNAs in the renal stroma lineage (FoxD1 Cre;Dicer), and performed a microarray analysis on E18.5 whole kidneys to determine the transcriptional changes.
Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival.
Specimen part
View Samples