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SRP069822
Mus musculus
164 Downloadable Samples
Illumina HiSeq 2500
Description
Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of the dynamic changes with age in the heterogeneous multipotent hematopoietic progenitor cell compartment, which regulates output of differentiated lymphoid cells. In this study, we observed progressive and specific loss of lymphoid-primed multipotent progenitor cells (LMPP/MPP4) as young animals began to age. Single cell RNA-seq revealed a concomitant increase in cycling of these progenitors with loss of a lymphoid priming signature. To interrogate functional multipotency of single cells, we developed a novel, feeder-free in vitro assay to concurrently assess lymphoid and myeloid potential. This assay revealed altered clonal composition of the LMPP/MPP4 compartment with aging, where progenitors with B cell and macrophage-restricted potential are lost while functionally multipotent progenitors are preserved. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging. Overall design: Examination of single cell RNA-seq transcriptomes in LMPP isolated from the bone marrow of 4mo and 14mo wild-type C57BL/6J female mice
Publication Title
Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 42 Downloadable Samples
- Illumina HiSeq 2000
Description
The goal of this study is to identify genomic signatures predicitve of cell-of-origin in acute myeloid leukemia 50K bulk leukemia (GFP+) cells from the spleen of recipient mice were sorted directly into 350µl of RLT buffer (Qiagen) and flash-frozen. Total RNA was isolated according to manufacturer’s protocols (Qiagen) including DNase treatment, and quality was assessed using an Agilent 2100 Bioanalyzer and RNA 6000 Nano kit. Amplified cDNA was sheared to approximately 300bp using a Covaris E220 Focused Ultrasonicator. RNA-seq library preparation used the TruSeq DNA sample prep kit v2 (Illumina). Libraries were sequenced on the Illumina HiSeq 2000 platform. Overall design: Transcriptome profiles of purified cell populations of hematopoetic stem and progenitor cells to identify transcriptomic singatures associated with leukemia cell-of-origin
Publication Title
Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The overarching goal of this study was to explore the antitumor activity of Z-endoxifen, a tamoxifen metabolite, with first-line endocrine therapies tamoxifen and letrozole in the letrozole-sensitive MCF7 aromatase expressing model (MCF7AC1), and with second-line endocrine therapies including tamoxifen, fulvestrant, exemestane, and exemestane plus everolimus, in letrozole-resistant MCF7 model (MCF7LR) in vivo.
Publication Title
Antitumor activity of Z-endoxifen in aromatase inhibitor-sensitive and aromatase inhibitor-resistant estrogen receptor-positive breast cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Gut dysbiosis is closely involved in the pathogenesis of inflammatory bowel disease (IBD). However, it remains unclear whether IBD-associated gut dysbiosis plays a primary role in disease manifestation or is merely secondary to intestinal inflammation. Here, we established a humanized gnotobiotic (hGB) mouse system to assess the functional role of gut dysbiosis associated with two types of IBD - Crohn's disease (CD) and ulcerative colitis (UC).
Publication Title
Functional Characterization of Inflammatory Bowel Disease-Associated Gut Dysbiosis in Gnotobiotic Mice.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The MUC1 oncoprotein is aberrantly overexpressed in diverse human malignancies including breast and lung cancer. Although MUC1 modulates the activity of several transcription factors, there is no information regarding the effects of MUC1 on global gene expression patterns and the potential role of MUC1-induced genes in predicting outcome for cancer patients. We have developed an experimental model of MUC1-induced transformation that has identified the activation of gene families involved in oncogenesis, angiogenesis and extracellular matrix remodeling. A set of experimentally-derived MUC1-induced genes associated with tumorigenesis was applied to the analysis of breast and lung adenocarcinoma cancer databases. A 35-gene MUC1-induced tumorigenesis signature (MTS) predicts significant decreases in both disease-free and overall survival in patients with breast (n = 295) and lung (n = 442) cancers. The data demonstrate that the MUC1 oncoprotein contributes to the regulation of genes that are highly predictive of clinical outcome in breast and lung cancer patients.
Publication Title
MUC1-induced alterations in a lipid metabolic gene network predict response of human breast cancers to tamoxifen treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Two nuclear 5'-3' exonucleases XRN2/3 in Arabidopsis thaliana are homologs of the yeast and human Rat1/Xrn2, which are involved in degradation and processing of several classes of nuclear RNAs and in transcription termination of RNA polymerase II. Here we show that knockdown of XRN3 leads to altered expression of several hundred of the Arabidopsis genes and accumulation of new non-coding RNAs. Using strand-specific short read sequencing we reveal a widespread accumulation of intergenic transcripts in xrn3 mutants. These non-coding XAT (xrn3-associated transcripts) RNAs are generated by Pol II read-through transcription and are usually polyadenylated and lack the 5' cap structure. We show that XRN3-mediated changes in expression of a subset of genes are related to XAT transcription and may be enhanced by XAT-mRNA chimeras produced in xrn3 plants while antisense XATs may trigger siRNA production. Our results highlight the important role of the Rat1/Xrn2 5'-3' exoribonucleases in the torpedo mechanism of Pol II transcription termination and show that a global disturbance in this process significantly impacts both gene expression and transcriptome integrity.
Publication Title
Defective XRN3-mediated transcription termination in Arabidopsis affects the expression of protein-coding genes.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Phytophthora sojae, Glycine max
- 14 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
Total RNA extracted from Phytophthora sojae (strain P6497) and infected soybean hypocotyls (cultivar Harosoy) provided template for synthesis of cDNA probes used in the microarray hybridizations. Infected plant hypocotyls were sampled 6 h, 12 h, 24 h, and 48 h after inoculation. Mycelia were grown on synthetic media (H&S) or vegetable juice media (V8). Zoospores were sampled at 0 h, 2 h and 6 h after inducing encystment and germination by agitation.
Publication Title
The Phytophthora sojae avirulence locus Avr3c encodes a multi-copy RXLR effector with sequence polymorphisms among pathogen strains.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 180 Downloadable Samples
- Illumina HiSeq 2000
Description
Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Background: Immune checkpoint blockade improves survival in a subset of patients with non-small cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. Methods: We performed comprehensive flow-cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). Results: Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of the PD-1 and TIM-3, and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function, and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, ~20% of cases had high B cell infiltrates with a subset producing IL-10. Conclusions: Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. Overall design: Single-cell comparison of normal and tumor infiltrated B-cells.
Publication Title
Multiparametric profiling of non-small-cell lung cancers reveals distinct immunophenotypes.
Sample Metadata Fields
Specimen part, Subject
View Samples