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SRP044917
Homo sapiens
27 Downloadable Samples
IlluminaHiSeq2000
Description
Next generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple negative breast cancers (TNBC, 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with pacitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI. Immunohistochemical staining of N1-ICD in TNBC xenografts correlated with responsiveness, and expression levels of the direct Notch target gene HES4 correlated with outcome in TNBC patients. Activating NOTCH1 point mutations were also identified in other solid tumors, including adenoid cystic carcinoma (ACC). Notably, ACC primary tumor xenografts with activating NOTCH1 mutations and high N1-ICD levels were sensitive to GSI, whereas N1-ICD low tumors without NOTCH1 mutations were resistant. Overall design: Gene expression profiling for Notch-sensitive cancer cell lines using RNA-seq, each sample with triplicates
Publication Title
Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Xenopus laevis
- 19 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones.
Publication Title
Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Local protein synthesis in sensory neuron axons is necessary for axonal regeneration with the efficiency of regeneration decreasing with age. Because the full repertoire of transcripts in embryonic and adult rat sensory axons is unknown we asked how the pool of mRNAs dynamically changes during ageing. We isolated mRNA from pure axons and growth cones devoid of non-neuronal or cell body contamination. Genome-wide microarray analysis reveals that a previously unappreciated number of transcripts are localised in sensory axons and that this repertoire changes during development toward adulthood. Embryonic sensory axons are enriched in transcripts encoding cytoskeletal-related proteins with a role in axonal outgrowth. Surprisingly, adult axons are highly enriched in mRNAs encoding immune molecules with a role in nociception. To validate our experimental approach we show that Tubulin-beta3 mRNA is present only in embryonic axons where it is locally synthesised. In summary, we show that the population of axonal mRNAs dynamically changes during development, which may partly contribute to the intrinsic capacity of axons at different ages to regenerate after injury and to modulate pain.
Publication Title
Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Illumina HiSeq 2500
Description
Embryonic CNS neurons can differentiate in culture and provide a model for maturation-related changes. A transcriptome profile over the course of maturation was perform to investigate the underlying molecular mechanism that drives maturation and its related changes such as developmental loss of intrinsic regenerative capacity. Overall design: Primary cortical neurons were excised from E18 rat embryos and were co-cultured with primary rat astrocytes from P0-2 rats. RNA were then extracted on day 1, 4, 8, 16, and 24 after plating.
Publication Title
Selective rab11 transport and the intrinsic regenerative ability of CNS axons.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 189 Downloadable Samples
Description
Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic lamina propria mesenchymal cells from 3 healthy donors. 183 single cell libraries, 6 bulk controls, 3 empty well controls. Individual donors processed as separate batches with Fluidigm C1 IFCs and pooled for sequencing (2 x Illumina HiSeq 2500 lanes).
Publication Title
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 162 Downloadable Samples
- Illumina HiSeq 4000
Description
Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Ulcerative colitis colonic lamina propria mesenchymal cells from 3 donors. 178 single cell libraries, 7 bulk controls, 7 empty well controls. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 4000 lane).
Publication Title
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 89 Downloadable Samples
- Illumina HiSeq 2500
Description
Intestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic epithelial cells from 3 healthy donors. 92 single cell libraries, 3 bulk controls, 1 empty well control. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 2500 lane).
Publication Title
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Sample Metadata Fields
Disease, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Identification of the role of retinoic acid on the activation of the dHSCs
Publication Title
Vitamin A-Retinoic Acid Signaling Regulates Hematopoietic Stem Cell Dormancy.
Sample Metadata Fields
Specimen part
View Samples