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SRP044668
Homo sapiens
94 Downloadable Samples
IlluminaHiSeq2000
Description
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.
Publication Title
MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in response to viruses and are essential for antiviral immune responses. Although related to classical dendritic cells (cDCs) in their development and expression profile, pDCs possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM) and emerge into peripheral lymphoid organs and tissues as fully differentiated cells. We now report that pDCs specifically express Runx2, a Runt family transcription factor that is essential for bone development. Runx2-deficient murine pDCs developed normally in the BM but were greatly reduced in the periphery. The defect was cell-intrinsic and was associated with the retention of mature Ly49Q+ pDCs in the BM. Runx2 was required for the expression of several pDC-enriched genes including chemokine receptors Ccr2 and Ccr5. Mature pDCs expressed high levels of Ccr5 at the surface, and Ccr5-deficient pDCs in a competitive setting were reduced in the periphery relative to the BM. Thus, Runx2 is required for the emergence of mature BM pDCs into the periphery, in a process that is partially dependent on Ccr5. These results establish Runx2 as a lineage-specific regulator of immune system development.
Publication Title
Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 391 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Histologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms.
Publication Title
Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 45 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This investigation provides a robust multi-dimensional compendium of gene expression data relevant to mouse facial development. It profiles the transcriptome ofectoderm and mesenchyme from the three facial prominences in a time series encompassing their growth and fusion. Analysis of the dataset identified more than 8000 differentially expressed genes comprising dramatically different ectoderm and mesenchyme programs. The mesenchyme programs included many genes identified in earlier analyses as well hundreds of genes not previously implicated in craniofacial development. The ectoderm programs included over a thousand genes that highlight epithelial structure, cell-cell interactions and signaling.
Publication Title
Systems biology of facial development: contributions of ectoderm and mesenchyme.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To investigate the extent of gene expression dysregulation by the human papillomavirus (HPV) oncoprotein E7, we performed global gene expression analysis on normal immortalized keratinocytes from skin (NIKS),
Publication Title
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the production of antibodies to self-nucleic acids, immune complex deposition and tissue inflammation such as glomerulonephritis. Innate recognition of molecular complexes containing self-DNA and RNA and the ensuing production of type I interferons (IFN) contribute to SLE development. Plasmacytoid dendritic cells (pDCs) have been proposed as a relevant source of pathogenic IFN in SLE; however, their net contribution to the disease remains unclear. We addressed this question using haplodeficiency of the pDC-specific transcription factor E2-2 (Tcf4), which causes a specific impairment of pDC function in otherwise normal animals. We report that Tcf4+/- animals were significantly protected from SLE-like disease caused by the overexpression of the endosomal RNA sensor Tlr7. The protection was also observed after the monoallelic deletion of Tcf4 specifically in the dendritic cell lineage. Furthermore, Tcf4 haplodeficiency in the B6.Sle1.Sle3 multigenic model of SLE ameliorated key disease manifestations including anti-DNA antibody production, immune activation and glomerulonephritis. These results provide genetic evidence that pDCs are critically involved in SLE pathogenesis, confirming their potential utility as therapeutic targets in the disease.
Publication Title
Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 282 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Kidney transplants that develop dysfunction or proteinuria after one year post transplant are at considerable risk for progression to renal failure. Identifying the molecules associated with graft failure could potentially lead to interventions that would slow the progression of organ failure.
Publication Title
A molecular classifier for predicting future graft loss in late kidney transplant biopsies.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
Publication Title
Molecular phenotypes of acute kidney injury in kidney transplants.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 3000
Description
Effector (Teff) and regulatory (Treg) CD4 T cells undergo metabolic reprogramming to support proliferation and immune function. While Phosphatidylinositide 3-kinase (PI3K)/Akt/mTORC1 signaling induces the glucose transporter Glut1 and aerobic glycolysis for Teff proliferation and inflammatory function, mechanisms that regulate Treg metabolism and function remain unclear. We show that TLR signals that promote Treg proliferation increase Glut1, PI3K/Akt/mTORC1 signaling, and glycolysis. However, TLR-induced mTORC1 signaling also impaired Treg suppressive capacity. Conversely, FoxP3 opposed PI3K/Akt/mTOR signaling to reduce glycolysis and anabolic metabolism while increasing oxidative and catabolic metabolism. Importantly, Glut1 expression was sufficient to increase Treg numbers but reduced suppressive capacity and FoxP3 expression. Thus, inflammatory signals and FoxP3 balance mTORC1 signaling and glucose metabolism to control Treg proliferation and suppressive function. Overall design: RNAseq of induced Glut1 transgenic and control Treg
Publication Title
Foxp3 and Toll-like receptor signaling balance T<sub>reg</sub> cell anabolic metabolism for suppression.
Sample Metadata Fields
Cell line, Subject
View Samples