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SRP154984
Homo sapiens
96 Downloadable Samples
Illumina HiSeq 4000
Description
Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection. Overall design: 96 nasal samples from healthy volunteers experimentally challenged with pneumococcus, 3 days after receiving live attenuated influenza vaccine or tetravalent inactivated influenza vaccine underwent RNA-Sequencing. Nasal cells were collected at baseline (D-4) before vaccination, and at 5 days after vaccination (or 2 days after pneumococcal inoculation, D+2) and at 12 days after vaccination (or 9 days after pneumoocccal inoculation, D9)
Publication Title
Inflammation induced by influenza virus impairs human innate immune control of pneumococcus.
Sample Metadata Fields
Specimen part, Disease stage, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Publication Title
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
This analysis represents the first comprehensive sampling of germ cells in the developing testis over time, at high-resolution, single-cell depth. From these analyses, we have not only revealed novel genetic regulatory signatures of murine germ cells over time, but have also demonstrated that cell types positive for a single marker gene have the capacity to change dramatically during testis maturation, and therefore cells of a particular “identity” may differ significantly from postnatal to adult life. Overall design: Single-cell suspensions of mammalian testes ranging from PND6 to adult were processed for single-cell RNAseq (10x Genomics Chromium) and libraries were sequenced on a NextSeq500 (Illumina).
Publication Title
Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing.
Sample Metadata Fields
Age, Disease, Cell line, Subject
View Samples- Homo sapiens
- 77 Downloadable Samples
- NextSeq 500
Description
We identified a rare subset of autoreactive lymphocytes with a hybrid phenotype of T and B cells including coexpression of TCR and BCR and key lineage markers of both cell types (hereafter referred to as dual expressers or DEs). To investigate the dual phenotype of DEs at single cell resolution, we examined their transcriptomes using single cell RNA sequencing (scRNA-seq). We sorted individual DEs, Bcon and Tcon cells from PBMCs of one type I diabetes patient and analyzed the transcriptomes of 34 DEs, 20 Bcon , and 23 Tcon using the plate-based SMART-seq2 protocol (Tirosh and Suva, 2018; Tirosh et al., 2016). Our results show that DEs have uniquely expressed genes along with genes encoding lineage markers of T and B cells. Overall design: Examination of the transcriptomes of three cell types, Des (Dual Expressors), Bcon (Conventional B) and Tcon (Conventional T) cells from the PBMCs of one type I diabetes patient
Publication Title
A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors.
Publication Title
Characterization of distinct immunophenotypes across pediatric brain tumor types.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 104 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To better understand the pathogenesis of acute promyelocytic leukemia (APL, FAB M3 AML), we identified genes that are expressed differently in APL cells compared to other acute myeloid leukemia subtypes, and to normal promyelocytes. Comparative gene expression analysis of 14 M3, 62 other AML (M0, M1, M2 and M4) and 5 enriched normal promyelocyte samples revealed a signature of 1,121 genes that are specifically dysregulated in M3 samples relative to other AML, and that do not simply represent normal promyelocyte expression (M3-specific signature). We used a novel, high throughput digital platform (Nanostring's nCounter system) to evaluate a subset of the most significantly dysregulated genes in 30 AML samples; 33 of 37 evaluable gene expression patterns were validated. In an additional analysis, we selected only genes that are dysregulated in M3 both compared to other AML subtypes, and to purified normal CD34+ cells, promyelocytes, and/or neutrophils, thereby isolating a 478 gene "composite M3 dysregulome". Surprisingly, the expression of only a few of these genes was significantly altered in PR-9 cells after PML-RARA induction, suggesting that most of these genes are not direct targets of PML-RARA. Comparison of the M3-specific signature to our previously described murine APL dysregulome revealed 33 commonly dysregulated genes, including JUN, EGR1, and TNF. Collectively, these results suggest that PML-RARA initiates a transcriptional cascade which generates a unique downstream expression signature in both primary human and mouse APL cells.
Publication Title
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.
Sample Metadata Fields
Sex, Race
View Samples- Bos taurus
- 88 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Establishment of an in vitro system to explore molecular mechanisms of mastitis susceptibility in cattle by comparative expression profiling of Escherichia coli and Staphylococcus aureus inoculated primary cells sampled from cows with different genetic predisposition for somatic cell score
Publication Title
Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score.
Sample Metadata Fields
Disease, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
sh RNA of p73 in Fibroblasts compared to non-silencing control
Publication Title
p73 poses a barrier to malignant transformation by limiting anchorage-independent growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared molecular characteristics of primary and recurrent pediatric ependymoma to identify sub-group specific differences.
Publication Title
Molecular sub-group-specific immunophenotypic changes are associated with outcome in recurrent posterior fossa ependymoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Engineering of genetically encoded calcium indicators predominantly focused on optimizing fluorescence changes, but effects of indicator expression on host organisms have largely not been addressed. Here, we report biocompatibility and wide-spread functional expression of the genetically encoded calcium indicator TN-XXL in a transgenic mouse model. To validate the model and to characterize potential effects of indicator expression we assessed both indicator function and a variety of host parameters such as anatomy, physiology, behavior and gene expression profiles in these mice. We also demonstrate the usefulness of primary cell types and organ explants prepared from these mice for imaging applications. While we do find mild signatures of indicator expression that may guide further indicator development the green indicator mice generated provide a well characterized resource of primary cells and tissues for in vitro and in vivo calcium imaging applications.
Publication Title
Biocompatibility of a genetically encoded calcium indicator in a transgenic mouse model.
Sample Metadata Fields
Specimen part
View Samples