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SRP095954
Caenorhabditis elegans
12 Downloadable Samples
Illumina HiSeq 2000
Description
The eukaryotic genome is organized in a three-dimensional structure called chromatin, constituted by DNA and associated proteins, the majority of which are histones. Post-translational modifications of histone proteins greatly influence chromatin structure and regulate many DNA-based biological processes. Methylation of lysine 36 of histone 3 (H3K36) is a post-translational modification functionally relevant during early steps of DNA damage repair. Here, we show that the JMJD-5 regulates H3K36 di-methylation and it is required at late stages of double strand break repair mediated by homologous recombination. Loss of jmjd-5 results in hypersensitivity to ionizing radiation and in meiotic defects, and it is associated with aberrant retention of RAD-51 at sites of double strand breaks. Analyses of jmjd-5 genetic interactions with genes required for resolving recombination intermediates (rtel-1) or promoting the resolution of RAD-51 double stranded DNA filaments (rfs-1 and helq-1) suggest that jmjd-5 prevents the formation of stalled postsynaptic recombination intermediates and favors RAD-51 removal. As these phenotypes are all recapitulated by a catalytically inactive jmjd-5 mutant, we propose a novel role for H3K36me2 regulation during late steps of homologous recombination critical to preserve genome integrity. Overall design: RNA sequencing of N2 and jmjd-5(tm3735) at 20C and 25C at generation 1 (G1) and generation 6 (G6)
Publication Title
JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Natural Killer (NK) cells are the first lymphocyte population to reconstitute early after non myelo-ablative and T cell-replete haploidentical hematopoietic stem cell transplantations (h-HSCTs) with post-transplant infusion of cyclophosphamide. The present study characterizes the transient and predominant expansion starting from the 2nd week after h-HSCT of a donor-derived unconventional subset of CD56dim/CD16neg (uCD56dim) NK cells expressing remarkable high levels of NKG2A and low levels of NKp46. Both transcription and phenotypic profiles indicated that uCD56dim NK cells are a distinct NK cell subpopulation with features of late differentiation, yet retaining proliferative capability and functional plasticity to generate conventional CD56bright/CD16pos NK cells in response to IL-15 plus IL-18. uCD56dim NK cells represent by far the largest NK cell subset detectable in the following 7 weeks after h-HSCT and they also express high levels of the activating receptors NKGD and NKp30 as well as of the lytic granules Granzyme-B and Perforin. Nonetheless, uCD56dim NK cells displayed a defective cytotoxicity that could be reversed by blocking the inhibitory receptor CD94/NKG2A. These data open new important perspectives to better understand the ontogenesis/homeostasis of human NK cells and to develop a novel immune-therapeutic approach by targeting the inhibitory NKG2A check point, thus enhancing NK cell alloreactivity early after h-HSCT.
Publication Title
The early expansion of anergic NKG2A<sup>pos</sup>/CD56<sup>dim</sup>/CD16<sup>neg</sup> natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
The inhibitory receptor Tim-3 has emerged as a critical regulator of the T cell dysfunction that develops in chronic viral infections and cancers. However, little is known regarding the signaling pathways that drive Tim-3 expression. Here, we demonstrate that IL-27 induces NFIL3, which promotes permissive chromatin remodeling of the Tim-3 locus and induces Tim-3 expression together with the immunosuppressive cytokine IL-10. We further show that the IL-27/NFIL3 signaling axis is crucial for the induction of Tim-3 in vivo. IL-27-conditioned Th1 cells exhibit reduced effector function and are poor mediators of intestinal inflammation. This inhibitory effect is NFIL3 dependent. In contrast, tumor-infiltrating lymphocytes (TILs) from IL-27R-/- mice exhibit reduced NFIL3, less Tim-3 expression and failure to develop dysfunctional phenotype, resulting in better tumor growth control. Thus, our data identify an IL-27/NFIL3 signaling axis as a key regulator of effector T cell responses via induction of Tim-3, IL-10, and T cell dysfunction.
Publication Title
An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
FOXE3 is a lens specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, we have identified DNAJB1 as a transcriptional target of FOXE3 in a novel pathway that is crucial for development of the anterior segment of the eye. Overall design: Human Embryonic Kidney (HEK293FT) cells were transfected with the expression vector (pT-RexTM-DEST30) harboring either the wild type or the mutant (C240*) FOXE3 ORF (open reading frame). The experimental design included a total of eight biological replicates of cells expressing the wild type and eight replicates of mutant FOXE3 along with eight non-transfected controls. Cells were harvested 24-hour post-transfection and subjected to total RNA isolation for the preparation of whole transcriptome next-generation sequencing libraries. Initially, we examined the quality of transcriptome libraries on a MiSeq genome analyzer. Subsequent to confirmation of the quality, all libraries were paired-end sequenced (2 x 100 bp) using Illumina TruSeq Cluster V3 flow cell at a concentration of 13.0 pM in two separate lanes (12 bar-coded mRNA pooled libraries in each lane) on a HiSeq 2000 genome analyzer.
Publication Title
FOXE3 contributes to Peters anomaly through transcriptional regulation of an autophagy-associated protein termed DNAJB1.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Rats were given pulmonary embolism by i.v. injection of 25 micron polystyrene microspheres or 0.01% Tween20 solution as vehicle control
Publication Title
Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The expression profiles of five human trunk level neural crest cell lines were determined on Affymetrix chips HG U133 Plus 2.0.
Publication Title
Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Sensorineural hearing loss affects the majority of the elderly population. Mammalian hair cells (HC) do not regenerate and current stem cell and gene delivery protocols result only in immature hair cells like-cells. For this reason, characterization of the transcriptional cascades that lead to development and survival of inner ear HC is essential for designing molecular-based treatments for deafness. We employed a cell type-specific approach to analyze the transcriptomes of the mouse early postnatal auditory and vestibular sensory epithelia and of hair cells derived from zebrafish model. Overall design: Murine auditory and vestibular epithelia were separated into hair-cells (HCs) and epithelial non-sensory cells (ENSCs) by flow cytometry. Gene expression levels were recorded in independent triplicates from the sorted cells using RNA-seq
Publication Title
RFX transcription factors are essential for hearing in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Sensorineural hearing loss affects the majority of the elderly population. Mammalian hair cells (HC) do not regenerate and current stem cell and gene delivery protocols result only in immature hair cells like-cells. For this reason, characterization of the transcriptional cascades that lead to development and survival of inner ear HC is essential for designing molecular-based treatments for deafness. We employed a cell type-specific approach to analyze the transcriptomes of the mouse early postnatal auditory and vestibular sensory epithelia and of hair cells derived from zebrafish model. Overall design: We utilized the ppv3b:GFP transgenic zebrafish, which express GFP predominantly in HC. We sorted GFP-positive and negative cells from 5 day post fertilization (dpf) larvae using flow cytometry, and profiled their transcriptomes using RNA-seq
Publication Title
RFX transcription factors are essential for hearing in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 45 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Time and dose related expression profiles of rat right heart tissue in microsphere bead model for Pulmonary embolism
Publication Title
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pulmonary vascular occlusions due to thromboemboli can result in pulmonary hypertension and right heart damage. Treatments to clear the vascular obstructions such as i.v. heparain or thrombolytics can resolve the hypertension but right ventricular damage often occurs first. Methods of protecting the right ventricle from hypertensive damage during the course of acute treatment to clear the thromboemboli are needed. Monocyte- and neutrophil-mediated inflammation and fibrosis are associated with chronic right ventricular damage but the pathways involved are not understood. A comprehesive survey of gene expression during chronic pulmonary embolism verses control rats has been conducted in this study.
Publication Title
Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats.
Sample Metadata Fields
Sex
View Samples