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SRP057984
Mus musculus
24 Downloadable Samples
Illumina HiSeq 2500
Description
Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function following myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors (Gata4, Hand2, Mef2c, and Tbx5=GHMT), we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process. Approximately 50% of reprogrammed fibroblasts displayed spontaneous beating after three weeks of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Igf1 and Pi3 kinase acted upstream of Akt, whereas mTORC1 and Foxo3a acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide new insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique. Overall design: We performed RNA-Seq using either isolated adult mouse ventricular cardiomyocytes (CMs) or MEFs treated for three weeks with empty vector, GHMT (iCMs cell sorted using aMHC-GFP before RNA-Seq), or AGHMT (iCMs cell sorted using aMHC-GFP before RNA-Seq).
Publication Title
Akt1/protein kinase B enhances transcriptional reprogramming of fibroblasts to functional cardiomyocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The formation of neuronal connections requires the precise guidance of developing axons towards their targets. In the Drosophila visual system, photoreceptor neurons (R cells) project from the eye into the brain. These cells are grouped into some 750 clusters comprised of eight photoreceptors or R-cells each. R cells fall into three classes, R1-R6, R7 and R8. Posterior R8 cells are the first to project axons into the brain. How these axons select a specific pathway is not known.
Publication Title
Robo-3--mediated repulsive interactions guide R8 axons during Drosophila visual system development.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Studies of aging and longevity are revealing how diseases that shorten life can be controlled to improve the quality of life and lifespan itself. Two strategies under intense study to accomplish this goal are rapamycin treatment and calorie restriction. New strategies are being discovered including one that uses low-dose myriocin treatment. Myriocin inhibits the first enzyme in sphingolipid synthesis in all eukaryotes and we showed recently that low-dose myriocin treatment increases yeast lifespan at least in part by down-regulating the sphingolipid-controlled Pkh1/2-Sch9 (ortholog of mammalian S6 kinase) signaling pathway.
Publication Title
Reducing sphingolipid synthesis orchestrates global changes to extend yeast lifespan.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
The goal of this study is to determine gene expression changes in the adult zebrafish spinal cord at 2 weeks after complete transection. Overall design: 2 samples were analyzed in duplicates: sham injured spinal cord and transected spinal cord at 2 weeks post-injury
Publication Title
Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 40 Downloadable Samples
- Illumina HiSeq 2000
Description
By contrast with mammals, adult zebrafish have a high capacity to regenerate damaged or lost myocardium through proliferation of spared cardiomyocytes. The epicardial sheet covering the heart is activated by injury and aids muscle regeneration through paracrine effects and as a multipotent cell source, and has received recent attention as a target in cardiac repair strategies. While it is recognized that epicardium is required for muscle regeneration and itself has high regenerative potential, the extent of cellular heterogeneity within epicardial tissue is largely unexplored. In this study, we performed transcriptome analysis on dozens of epicardial lineage cells purified from zebrafish harboring a transgenic reporter for the pan-epicardial gene tcf21. Hierarchical clustering analysis suggested the presence of at least three epicardial cell subsets defined by expression signatures. We validated many new pan-epicardial and epicardial markers by alternative expression assays. Additionally, we explored the function of the scaffolding protein and main component of caveolae, caveolin-1 (cav1), which was present in each epicardial subset. In BAC transgenic zebrafish, cav1 regulatory sequences drove strong expression in ostensibly all epicardial cells and in coronary vascular endothelial cells. Moreover, cav1 mutant zebrafish generated by genome editing showed grossly normal heart development and adult cardiac anatomy, but displayed profound defects in injury-induced cardiomyocyte proliferation and heart regeneration. Our study defines a new platform for the discovery of epicardial lineage markers, genetic tools, and mechanisms of heart regeneration. Overall design: Deep sequencing of isolated single epicardial cells
Publication Title
Single epicardial cell transcriptome sequencing identifies Caveolin 1 as an essential factor in zebrafish heart regeneration.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Promoter methylation was assayed in a number of breast cancer and control normal samples along with the effects of 5'-aza-2'-deoxycytidine on breast cancer cell line transcriptomes.
Publication Title
Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Danio rerio
- 14 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
We compared transcriptional profiles of regenerating zebrafish caudal fins following fin amputation with profiles from uninjured zebrafish caudal fins Overall design: Examination of whole fin transcriptional profiles from regenerating fins (2 pools of 10 fins) and uninjured fins (2 pools of 10 fins)
Publication Title
Modulation of tissue repair by regeneration enhancer elements.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
We compared transcriptional and chromatin profiles of regenerating zebrafish hearts following genetic ablation with profiles from uninjured zebrafish hearts. Overall design: Examination of whole heart transcriptional profiles from ablated hearts (2 pools of 10 hearts) and uninjured hearts (2 pools of 10 hearts). Examination of differential H3K27Ac marks following genetic ablation of cardiomyocytes (regenerating hearts) and uninjured hearts.
Publication Title
Modulation of tissue repair by regeneration enhancer elements.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Senescence is a state of stable cell cycle exit that has important implications for development, physiology and disease. It is distinct from quiescence in which cells can be induced to re-enter the cell cycle. Although it is well known that there are massive changes in the heterochromatin of senescent cells, the molecular mechanisms underpinning the transition from reversible quiescence into irreversible senescence have remained elusive. Here, we demonstrate that the chromatin-remodeling enzyme ATRX is required for senescence. ATRX accumulates in nuclear foci during both replicative and cellular senescence. Using ChIP-seq and RNA-seq we identified HRAS as part of an ATRX regulated gene expression program associated with senescence. Repression of HRAS is sufficient to promote the transition of quiescent cells into senescence. Thus we conclude that the repression of HRAS is likely a direct consequence of ATRX binding and critical to how it mediates its role in senescence. Overall design: mRNA expression profiles were analyzed in dedifferentiated liposarcoma cell lines under cycling, quiescent and senescent (using two unique inducers) conditions via RNA-seq
Publication Title
ATRX is a regulator of therapy induced senescence in human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alveolar macrophages from never smokers and active smokers were isolated by bronchoalveolar lavage and gene expression was measured. Chronic cigarette smoke exposure, as occurs in smoker's lungs, leads to significant changes in gene expression. Of note, RNA was isolated immediately following bronchoscopy. Alveolar macrophage levels were >95%.
Publication Title
Cigarette smoking decreases global microRNA expression in human alveolar macrophages.
Sample Metadata Fields
Specimen part
View Samples