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SRP186407
Mus musculus
2 Downloadable Samples
Illumina HiSeq 4000
Description
In many forms of retinal degenerative diseases in human, microglia relocate to and accumulate in the subretinal space. However, the roles of microglia in retinal degeneration are poorly understood. By leveraging single cell RNA-seq, we identified a distinct microglia subtype in the subretinal space. These microglia underwent transcriptional reprogramming characterized by reduced expression of homeostatic checkpoint genes and upregulation of injury-responsive genes. Importantly, this transition is associated with protection of the retinal pigment epithelium from damage caused by disease. Therefore, our data demonstrated microglial heterogeneity in retinal degeneration and may provide important implications for developing new strategies to prevent loss of vision. Overall design: Transcriptional profiling of Cx3cr1+ single cells from the mouse model of light-induced retinal degeneration with matched control, generated from single cell RNA-sequencing of over 10,000 cells.
Publication Title
Microglial Function Is Distinct in Different Anatomical Locations during Retinal Homeostasis and Degeneration.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple signaling pathways, structural proteins and transcription factors are involved in regulation of endothelial barrier function. The Forkhead protein FOXF1 is a key transcriptional regulator of lung embryonic development, and we use a conditional knockout approach to examine the role of FOXF1 in adult lung homeostasis and lung injury and repair. Tamoxifen-regulated deletion of both Foxf1 alleles in endothelial cells of adult mice (Pdgfb-iCreER/Foxf1 caused lung inflammation and edema, leading to respiratory insuffency and uniform mortality. Deletion of a single foxf1 allele was sufficient to increase susceptibility of heterozygous mice to acute lung injury. FOXF1 abundance was decreased in pulmonary endothelial cells of human patients with acute lung injury. Gene expression analysis of pulmonary endothelial cells of FOXF1 deletion indicated reduced expression for genes critical for maintance and regulation of adherens junctions. FOXF1 knockdown in vitro and in vivo disrupted adherens junctions, increased lung endothelial permeability, and the abundance of mRNA and protein for sphingosine 1 phosphate receptor 1 (S1PR1), a key regulator of endothelial barrier function. Chromatin immunoprecipitation and luciferase reporter assay demonstrated that FOXF1 directly bound to and induced the tanscriptional activity of the S1pr1 promoter. Pharmacological administratiion of S1P to injured pdgfb-iCreER/Foxf1 mice restored endothelial barrier function, decreased lung edema and improved survival. Thus, FOXF1 promotes normal lung homeostasis and lung repair, at least in part, by enhancing endothelial barrier function through transcriptional activation of the S1P/S1PR1/ signaling pathway. Overall design: RNA was isolated and pooled from the lungs of multiple mice with either the Foxf1 floxed alleles alone or Pdgfb-iCreER Foxf1 floxed mice.
Publication Title
FOXF1 maintains endothelial barrier function and prevents edema after lung injury.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Myotonic dystrophy type 1 (DM1) is a dominantly inherited disease that affects multiple organ systems. Cardiac dysfunction is the second leading cause of death in DM1. We quantified gene expression in heart tissue from a heart-specific DM1 mouse model (EpA960/MCM) which inducibly expresses human DMPK exon 15 containing 960 CUG expanded repeats and that reproduced Celf1 up regulation. To assess if, in addition to splicing and miRNA defects, CUGexp RNA also perturbed the steady state mRNA levels of genes, we carried out a microarray study on wildtype E14, adult, MCM controls and DM1 mouse hearts. As anticipated we noted a large number of genes to be developmentally regulated in wildtype hearts, however, within 72h of induction of CUGexp RNA there appeared to be a coordinate adult-to-embryonic shift in steady state levels of many genes.
Publication Title
The Mef2 transcription network is disrupted in myotonic dystrophy heart tissue, dramatically altering miRNA and mRNA expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Hepatic fibrosis is the common end stage to a variety of chronic liver injuries and is characterized by an excessive deposition of extracellular matrix (ECM), which disrupts the liver architecture and impairs liver function. The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblasts transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated aSMACreER;Foxf1fl/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1a2, Col5a2, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro. Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs. Overall design: RNAseq on isolated hepatic stromal cells from Foxf1 fl/fl and aSMACreER;Foxf1 fl/fl mice after 5 weeks of carbon tetrachloride-induced liver injury.
Publication Title
The Forkhead box F1 transcription factor inhibits collagen deposition and accumulation of myofibroblasts during liver fibrosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 66 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000, Illumina Genome Analyzer II
Description
Alternative cleavage and polyadenylation (APA) results in mRNA isoforms containing different 3' untranslated regions (3'UTRs) and/or coding sequences. How core cleavage and polyadenylation (C/P) factors regulate APA is not well understood. Using siRNA knockdown coupled with deep sequencing, we found that several C/P factors can play significant roles in 3'UTR-APA. Whereas Pcf11 and Fip1 enhance usage of proximal poly(A) sites (pAs), CFI-25/68, PABPN1, and PABPC1 promote usage of distal pAs. Strong cis element biases were found for pAs regulated by CFI or Fip1, and the distance between pAs plays an important role in APA regulation. In addition, intronic pAs are substantially regulated by splicing factors, with U1 mostly influencing C/P events in 5' introns and U2 impacting those in efficiently spliced introns. Furthermore, PABPN1 regulates expression of transcripts with pAs near the transcription start site, a property possibly related to its role in RNA degradation. Finally, we found that groups of APA events regulated by C/P factors are also modulated in cell differentiation and development with distinct trends. Together, our results indicate that the abundance of different C/P factors and splicing factors plays diverse roles in APA, and is relevant to APA regulation in biological conditions. Overall design: knockdown experiments of 23 C/P factors, 3 splicing factors and U1D in mouse C2C12 myoblast cells
Publication Title
Systematic profiling of poly(A)+ transcripts modulated by core 3' end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcription factor FoxM1 is expressed in proliferating cells, and its expression is critical for cell proliferation in embryos and tumors. FoxM1 regulates a multi-gene transcriptional network for cell cycle regulation.
Publication Title
Forkhead box M1 transcriptional factor is required for smooth muscle cells during embryonic development of blood vessels and esophagus.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The highly conserved Wnt signaling pathway drives intestinal homeostasis across species. Apc is a negative regulator of Wnt signaling. Loss of function mutations in Apc are found in 80-90% of human colorectal cancers. Importantly, Apc loss is widely known as the key driving event in the disease.
Publication Title
Intestinal stem cell overproliferation resulting from inactivation of the APC tumor suppressor requires the transcription cofactors Earthbound and Erect wing.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Identification of genes that are differentially regulated in fibroblasts derived from dysplastic oral mucosa and oral squamous cell carcinoma compared to fibroblasts derived from normal oral mucosa.
Publication Title
Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Early chemotherapy for advanced/metastatic non-castration resistant prostate cancer (PCa) may improve overall patient survival. We studied the safety, tolerability and early efficacy of up-front docetaxel chemotherapy and androgen deprivation therapy (ADT) versus ADT alone for patients with newly-diagnosed advanced/metastatic PCa. As proof of concept, we undertook in vivo gene expression profiling by next generation RNA sequencing (RNA-Seq). Overall design: Tumour biposies from 6 patients were taken before and after treatment with combined ADT and docetaxcel for 6 weeks
Publication Title
Identification of a candidate prognostic gene signature by transcriptome analysis of matched pre- and post-treatment prostatic biopsies from patients with advanced prostate cancer.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Macaca mulatta
- 7 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Goal of this study was to assess the levels of protection and investigate cellular, humoral, and mucosal immune correlates on the functional and gene transcriptional levels in elite-controller macaques following high dose SIV challenge.
Publication Title
Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge.
Sample Metadata Fields
Specimen part
View Samples