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GSE38609
Homo sapiens
28 Downloadable Samples
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2), Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Brain transcriptional and epigenetic associations with autism.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2), Illumina HumanHT-12 V4.0 expression beadchip
Description
Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
Publication Title
Brain transcriptional and epigenetic associations with autism.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 22 Downloadable Samples
Illumina HiSeq 2500
Description
Calorie restriction (CR) enhances longevity and mitigates aging phenotypes in numerous species. Physiological responses to CR are cell-type specific and variable throughout the lifespan; however, the mosaic of molecular changes responsible CR benefits remain unclear, particularly in brain regions susceptible to deterioration throughout aging. Thus, we examined the influence of long-term CR on the CA1 hippocampal region, a key learning and memory brain area that is vulnerable to age-related pathologies, such as Alzheimer’s disease (AD). Through mRNA sequencing and NanoString nCounter analysis, we demonstrate that one year of CR feeding suppresses an age-dependent signature of 882 genes functionally associated with synaptic transmission-related pathways, including calcium signaling, long-term potentiation (LTP), and Creb signaling in wild-type mice. By comparing the influence of CR on hippocampal CA1 region transcriptional profiles at younger- (5 months) and older-adult (15 months) timepoints, we identify conserved upregulation of proteome quality control and calcium buffering genes, including heat shock 70 kDa proteins 1b and 5 (Hspa1b and Hspa5), protein disulfide isomerase family A members 4 and 6 (Pdia4 and Pdia6), and calreticulin (Calr). Expression levels of putative neuroprotective factors, klotho (Kl) and transthyretin (Ttr), are also elevated by CR throughout adulthood, although the global CR-specific expression profiles at young and older timepoints are highly divergent. At a previously unachieved resolution, our results demonstrate conserved activation of neuroprotective gene signatures and broad CR-suppression of age-dependent hippocampal CA1 region expression changes, indicating that CR functionally maintains a more youthful transcriptional state within hippocampal CA1 throughout aging. Overall design: Hippocampal CA1 region mRNA profiles of younger- (5 months) and older-adult (15 months) mice on calorie-restricted (CR) and normal (AD) diets were generated by deep sequencing using Illumina HiSeq 2500.
Publication Title
Calorie Restriction Suppresses Age-Dependent Hippocampal Transcriptional Signatures.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Full title: Prepubertal Human Spermatogonia and Mouse Gonocytes Share Conserved Gene Expression of Germline Stem Cell Regulatory Molecules
Publication Title
Prepubertal human spermatogonia and mouse gonocytes share conserved gene expression of germline stem cell regulatory molecules.
Sample Metadata Fields
Age
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: RNA-Seq analysis can help identify large set of differentially expressed genes at a time. We performed RNA-Seq analysis to identify differentially expressed genes in the PBMCs of war veterans suffering from PTSD. Methods: Total RNA from PBMCs from PTSD +ve and -ve individuals were used for RNA-Seq analysis. Results: We obtained, on average, ~60 millions reads per sample. More than 70% of the reads were mapped to human genome. Functional analysis of the differentially expressed genes (362) revealed dysregulation in immune system network. Conclusions: Our present study provides further proof that immune system related genes and pathways are dysregulated in PTSD PBMCs. Overall design: RNA-Seq was performed with RNA from 5 each control and PTSD individuals. PBMCs collected within one hour of blood draw were used for RNA isolation. 1 ug of total RNA was used for library synthesis and sequenced in a HighSeq 2000 illumina instrument at Tufts University.
Publication Title
Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop because ECs are difficult to culture and little is known about how to sustain their vascular identity and direct them to form long-lasting new vessels or engraft into existing ones. We found that multiple non-vascular cell types transiently expressed EC markers after enforced expression of the transcription factors, Etv2, Erg, and Fli1. However, only mid-gestational amniotic cells could be converted to cells that maintained EC gene expression and proliferated in culture to yield billions of vascular cells. Even so, these converted cells performed sub-optimally in assays of EC function. We used constitutive Akt signaling to mimic the shear forces of the vascular environment and promote EC survival in an effort to correct the deficiencies of the converted cells. Akt signaling increased gene expression of EC morphogenesis genes, including Sox17, shifted the genomic targeting of Fli1 to favor nearby Sox consensus sites, and enhanced the in vivo vascular function of EC-like converted cells. Enforced expression of Sox17 was dispensable for broad EC gene activation, but indispensable for vascular engraftment and reperfusion of ischemic tissue. Our results identify a transcription factor network comprised of Ets and Sox17 factors that specifies and sustains endothelial cell fate and function. This work shows that the commonly used criterion of transcriptional similarity for cell conversion can fail to predict in vivo vascular function. Our approach shows that stringent functional testing in vitro and in vivo is necessary to validate engineered endothelial cell grafts. Overall design: Transcriptome sequencing of endothelial cells and amniotic cells
Publication Title
Sox17 drives functional engraftment of endothelium converted from non-vascular cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Cdx2/IL-1beta mice have less intestinal metaplasia at the squamocolumnar junction thanIL-1beta mice alone.
Publication Title
Immature myeloid progenitors promote disease progression in a mouse model of Barrett's-like metaplasia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch’s membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Methods: ECs from P5 and P30 mice were labeled in vivo by retro-orbital injection of fluorescently-labeled anti-VE-Cadherin. After 10 minutes, mice were euthanized, eyeballs were enucleated and the anterior segment was discarded. After removal of the neural retina, RPE/choroid was mechanically dissected from the sclera and digested. ECs were isolated by flow cytometry and processed immediately for RNA extraction. Results: Transcriptome analyses show that whereas P5 choroid EC transcriptome is preferentially enriched in cell cycle- and chromosome-related transcripts, reflecting an immature phenotype, the transcriptome of adult (P30) choroid ECs is enriched in genes encoding proteins involved in ‘biological adhesion’, including a variety of extracellular matrix (ECM)-related genes. Conclusion: these results strongly suggest that mature choroid ECs actively participate in extracellular matrix assembly and regulation. Overall design: Transcriptome of choroid ECs isolated from P5 and P30 mice (3 independent isolations, 7 animals per isolation) was determined using the Illumina HiSeq2000 platform. Upon quality control using FastQC, raw reads were aligned to the mouse genome (mm9) using TopHat with default parameters. CuffLinks with GC and upper quartile normalization was then used to calculate normalized expression levels.
Publication Title
Concerted regulation of retinal pigment epithelium basement membrane and barrier function by angiocrine factors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus, Homo sapiens
- 57 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Endothelial cells from nine steady state tissues and two regenerating tissues (bone marrow and liver) were intravitally labeld, isolated via flow sorting, and immediately processed for RNA extraction.
Publication Title
Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Developmental pathways that orchestrate the fleeting transition of endothelial cells into haematopoietic stem cells remain undefined. Here we demonstrate a tractable approach for fully reprogramming adult mouse endothelial cells to haematopoietic stem cells (rEC-HSCs) through transient expression of the transcription-factor-encoding genes Fosb, Gfi1, Runx1, and Spi1 (collectively denoted hereafter as FGRS) and vascular-niche-derived angiocrine factors. The induction phase (days 0-8) of conversion is initiated by expression of FGRS in mature endothelial cells, which results in endogenous Runx1 expression. During the specification phase (days 8-20), RUNX1+ FGRS-transduced endothelial cells commit to a haematopoietic fate, yielding rEC-HSCs that no longer require FGRS expression. The vascular niche drives a robust self-renewal and expansion phase of rEC-HSCs (days 20-28). rEC-HSCs have a transcriptome and long-term self-renewal capacity similar to those of adult haematopoietic stem cells, and can be used for clonal engraftment and serial primary and secondary multi-lineage reconstitution, including antigen-dependent adaptive immune function. Inhibition of TGF? and CXCR7 or activation of BMP and CXCR4 signalling enhanced generation of rEC-HSCs. Pluripotency-independent conversion of endothelial cells into autologous authentic engraftable haematopoietic stem cells could aid treatment of haematological disorders. Overall design: Expression profiling by high throughput sequencing data; GPL17021 Illumina HiSeq 2500 (Mus musculus)
Publication Title
Conversion of adult endothelium to immunocompetent haematopoietic stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples