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GSE21535
Bos taurus
22 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
The objective was to study the transcriptomic changes in adipose tissue in the early stages of lactation, specifically in Bos Taurus, Holstein dairy cattle as a function of milk production and genetic merit.
Publication Title
Differential expression of genes in adipose tissue of first-lactation dairy cattle.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
The epigenetic regulator BMI1 is upregulated in many human malignancies and has been implicated in cell migration, but the impact on autochthonous tumor progression is unexplored. Our analyses of human expression data show that BMI1 levels increase with progression in melanoma. We find that BMI1 expression in melanoma cells does not influence cell proliferation or primary tumor growth. In contrast, BMI1 levels are a key determinant of melanoma metastasis, whereby deletion impairs and overexpression enhances dissemination. Remarkably, BMI1’s pro-metastatic effect reflects enhancement of all stages of the metastatic cascade including invasion, migration, extravasation, adhesion and survival. Additionally, downregulation or upregulation of BMI1 induces sensitivity or resistance to BRAF inhibitor. Consistent with these pleiotropic effects, we find that BMI1 promotes widespread gene expression changes that encompass key hallmarks of the melanoma invasive signature, including activation of TGFß, non-canonical Wnt, EMT and EGF/PDGF pathways. Importantly, for both primary and metastatic melanoma samples, this BMI1-induced signature identifies invasive subclasses of human melanoma and predicts poor patient outcome. Our data yield key insights into melanoma biology and establish BMI1 as a compelling drug target whose inhibition would suppress both metastasis and chemoresistance. Overall design: Three replicates of A375 BMI1 or GFP overexpressing cells.
Publication Title
BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. We used kinetic microarray, Northern Blotting and bioinformatics analysis of IL-3 dependent myeloblasts to determine whether IL-3 acts in part by regulating the rate of turnover of mRNA transcripts in specific functional pathways. Our results indicate that exposure of myeloblasts to IL-3 causes immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Examples include transcripts associated with proliferation and leukemic transformation (pik3cd, myb, pim-1), hematopoietic development (cited2), differentiation control (cdkn1a) and RNA processing (BRF1, BRF2). A domain in the 3-utr of IL-6 that mediates IL-3 responsiveness contains AU-rich elements that bind proteins known to modulate mRNA stability, however a known destabilizing protein (AUF1) is shown not to mediate degradation in the absence of IL-3. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of this network of transcripts could contribute to growth patterns observed in leukemia.
Publication Title
IL-3 and oncogenic Abl regulate the myeloblast transcriptome by altering mRNA stability.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Previous work has suggested that the imprinted gene Phlda2 regulates the signalling function of the placenta by modulating the size of the endocrine compartment. This study investigated the affect that Phlda2 mutant placenta has upon the brains of the wildtype dams carrying different placenta and consequently offspring.
Publication Title
Maternal care boosted by paternal imprinting in mammals.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina HiSeq 2500
Description
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: CD4+ T helper cells were sorted as naive T cells (CD4+CD25-CD45RA+), Treg (CD4+CD25+IL7Rlo), Th1 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6-), Th2 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6-), Th17 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6+), Th1-17 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6+), and Tfh subsets (CXCR5+ counterparts of each). RNA-seq cDNA library construction was performed using the SMART-Seq v4 Ultra Low Input RNA Kit (Clontech) with 2?ng of input RNA. Sequencing libraries were prepared using the Nextera XT DNA Library Prep Kit (Illumina).
Publication Title
Clonal replacement of tumor-specific T cells following PD-1 blockade.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
Description
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: Dissociated tumor samples were sorted as either CD45+ CD3+ tumor-infiltrating T cells, other CD45+ CD3- tumor-infiltrating lymphocytes and CD45- CD3- tumor/stromal cells. Sorted cells were subjected to paired single cell RNA- and TCR-sequencing on the droplet based 10X Genomics platform.
Publication Title
Clonal replacement of tumor-specific T cells following PD-1 blockade.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 1000
Description
To investigate the function of HSP20 in adipogenesis and thermogenesis of white adipose tissue. Overall design: Total RNA were extracted from inguinal white adipose tissue of 6 mice (12 weeks old, 3 Hsp20 knockout, 3 wild type in C57BL/6 background as control).
Publication Title
An Hsp20-FBXO4 Axis Regulates Adipocyte Function through Modulating PPARγ Ubiquitination.
Alternate Accession IDs
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression data from CD22+B220+ FACS-purified splenocytes of adult Sca1-HGAL knock-in CBAxC57BL/6J mice or wild-type littermates.
Publication Title
Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 170 Downloadable Samples
- Illumina HiSeq 1000
Description
Purpose: Single-cell whole transcriptome sequencing was used to better understand the mechanism of action of our Dyrk1a inhibitor''s proliferation of pancreatic islets. Methods: primary pancreatic islets were isolated, cultured, and stimulated with either 0.1% DMSO or 3 µM GNF4877. Single cells were captured and cDNA isolated on a Fluidigm C1 instrument. Sequencing libraries were made with Nextera XT reagents (Illumina) and single-end 50 bp reads were generated on an Illumina HiSeq 1000. Reads were mapped to the rat transcriptome. Results: Consistent with GNF4877 eliciting beta cell proliferation, we observed an increase in the number of beta cells co-expressing insulin 1 and genes involved in cell cycle including the M phase marker Cyclin B1. Comparison of Cyclin B1 expressing cells from GNF4877-treated islets to beta cells from DMSO-treated islets further revealed a significant increase expression of genes associated with full cell cycle progression and enrichment of Gene Ontology (GO) categories for proliferation. Conclusions: Since only a small subset of islet cells proliferate when stimulated with GNF4877, single-cell transcriptome sequencing allowed us to examine expression of genes co-regulated with known proliferation markers and will hopefully allow us to characterize beta cell subsets which are responsive to proliferation-associated therapies. Overall design: 84 GNF4877-treated and 86 DMSO-treated rat islet cells containing greater than 100,000 mapped sequencing reads per cell and having a single verified cell per port were compared
Publication Title
Inhibition of DYRK1A and GSK3B induces human β-cell proliferation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Cancer incidence increases in the elderly, although the underlying reasons for this association are unknown. We show that B-progenitors in old mice exhibit profound signaling and metabolic defects, and that expression of BCR-ABL, NRASV12 and MYC reverses these fitness defects, leading to selection of oncogenically-initiated cells and leukemogenesis in old hematopoietic backgrounds. Aging is associated with increased inflammation in the BM microenvironment, and inducing inflammation in young mice phenocopies aging B-lymphopoiesis. Importantly, reducing inflammation in aged mice preserves the function of B-progenitors and prevents NRasV12-mediated oncogenesis. We conclude that chronic microenvironments in old age lead to reductions in the fitness of hematopoietic stem and progenitor cell populations. This reduced progenitor pool fitness leads to selection for cells harboring oncogenic mutations in part due to their ability to correct aging-associated functional defects.
Publication Title
Aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors.
Alternate Accession IDs
Sample Metadata Fields
Age, Specimen part
View Samples