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SRP070670
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
- 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- 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- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The purpose of this study is to compare the transcriptome expression profiles of E13.5 Foxf2-/-;Osr2RFP/+ and control palatal mesenchyme by using RNA-seq analysis. Methods: Foxf2+/- female mice were crossed with Foxf2+/-;Osr2RFP/+ male mice.The embryos were harvested at E13.5. The pair of palatal shelves were dissected from each Osr2-RFP+ embryo. The RFP+ palatal mesenchyme cells were isolated by using fluorescence-activated cell sorting (FACS). RNA-seq analysis was carried out using the FACS-isolated palatal mesenchyme from Foxf2-/-;Osr2RFP/+, Foxf2+/-;Osr2RFP/+ and Osr2RFP/+embryos, respectively. Overall design: The transcriptome expression profiles of E13.5 control and Foxf2-/-Osr2RFP/+ palatal mesenchyme by using RNA-seq analysis, in duplicates, using Illumina HisEq 2000.
Publication Title
A Shh-Foxf-Fgf18-Shh Molecular Circuit Regulating Palate Development.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 50 Downloadable Samples
- Affymetrix Rat Clariom S Assay (clariomsrat), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Rattus norvegicus
- 50 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Rat Clariom S Assay (clariomsrat)
Description
As a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 months. We found that most transcriptional changes occur at 1 and 3 months after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 months. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. This data suggests that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.
Publication Title
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
MHC class I-related molecule MR1 presents riboflavin-derived microbial metabolites and folate-derivatives to mucosal-associated invariant T cells, but it is unknown whether MR1 can bind alternative antigens that stimulate other T cell lineages. Here we report that human T cells displaying diverse TCR-a and ß chains recognize MR1-expressing cells in the absence of microbial ligands and respond to recombinant MR1 molecules loaded with antigens extracted from stimulatory targets. Transcriptome analysis revealed functional heterogeneity of MR1-reactive T cells (MR1T cells), which displayed differential expression of various transcription factors regulating T cell polarization, proliferation and apoptosis. Accordingly, MR1T cells displayed multiple profiles of chemokine receptor expression and secreted variable combinations of cytokines and growth factors, suggesting a diversity of immunological roles across numerous tissues. Functionally, MR1T cells were capable of inducing dendritic cell maturation and stimulating anti-microbial responses in intestinal epithelial cells. These data demonstrate that MR1 presents endogenous antigens to a novel population of functionally diverse human T cells. Overall design: mRNA profiles of two representative MR1T cell clones in resting (not exposed to antigen) and activated (stimulated with A375-MR1 antigen target cells and activated) states
Publication Title
Functionally diverse human T cells recognize non-microbial antigens presented by MR1.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HESC-H9 and iPSC lines 3.5, 3.6 and 3.12 were analyzed using Affymetrix microarray before and after Definitive Endoderm (DE) formation. DE was induced using the ActivinA differentiation protocol described by D'Amour et al., 2006 (PMID: 16258519) Clustering analysis of transcripts that were differentially regulated during DE formation indicated that iPSC lines 3.5 and 3.12 differentiate in manner that is highly similar to HESC-H9 cells iPSC line 3.6 had a more divergent transcriptional profile.
Publication Title
Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
We report single cell expression in mouse young and old aorta endothelial cells. These data provide insight in the gene expression related to regeneration of mouse aorta endothelial layer. Overall design: Single cell RNA sequencing was done on a young mouse (8 weeks) and an old mouse (18 months), 10X Genomics Single Cell 3' v2 was used.
Publication Title
Endothelial Regeneration of Large Vessels Is a Biphasic Process Driven by Local Cells with Distinct Proliferative Capacities.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- IlluminaHiSeq2000
Description
Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize conserved bacterial antigens derived from riboflavin precursors, presented by the non-polymorphic MHC class I-like molecule MR1. Here, we show via transcriptomic analysis that human MAIT cells are remarkably oligoclonal in both blood and liver, display high inter-individual homology, and exhibit a restricted length CDR3ß domain of the TCRVß chain. We extend this analysis to a second sub-population of MAIT cells expressing a semi-invariant TCR conserved between individuals. Overall design: Study of CDR3 regions of TCRalpha and beta sequences
Publication Title
Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire.
Sample Metadata Fields
No sample metadata fields
View Samples