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SRP048836
Mus musculus
2 Downloadable Samples
Illumina HiSeq 2500
Description
Hox genes are required during the morphogenesis of both vertebrate digits and external genitals.We investigated whether transcription in such distinct contexts involves a shared enhancer-containing landscape. We show that the same regulatory topology is used, yet with some tissue-specific enhancer-promoter interactions, suggesting the hijacking of a regulatory backbone from one context to the other. In addition, comparable organizations are observed at both HoxA and HoxD clusters, which separated through genome duplication in an ancestral invertebrate animal.We propose that this convergent regulatory evolution was triggered by the pre-existence of some chromatin architecture, thus facilitating the subsequent recruitment of the appropriate transcription factors. Such regulatory topologies may have both favored and constrained the evolution of pleiotropic developmental loci in vertebrates. Overall design: RNA-seq from mouse E12.5 digits cells and mouse E15.5 genital tubercle cells.
Publication Title
Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and, subsequently, into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating processes of these two regulatory domains. We propose a model whereby the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition. Overall design: RNA-seq analysis of proximal and distal forelimbs from E12.5 wt or Hoxa13-/-;Hoxd13-/- mutant embryos
Publication Title
A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The molecular mechanisms underlying the great differences in susceptibility to noise-induced hearing loss (NIHL) exhibited by both humans and laboratory animals are unknown. Using microarray technology, the present study demonstrates that the effects of noise overexposure on the expression of molecules likely to be important to the development of NIHL differ among inbred mice that have distinctive susceptibilities to NIHL including B6.CAST, 129X1/SvJ, and 129S1/SvImJ. The noise-exposure protocol produced, on average, a permanent loss of about 40 dB in sensitivity for auditory brainstem responses in susceptible B6.CAST mice, but no threshold elevations for the two resistant 129S1/SvImJ and 129X1/SvJ substrains. Measurements of noise-induced gene expression changes 6 h after the noise exposure revealed significant alterations in the expression levels of 48 genes in the resistant mice, while by these same criteria, there were seven differentially expressed genes in the susceptible B6.CAST mice. Differentially expressed genes in both groups of mice included subsets of transcription factors. However, only in the resistant mice was there a significant induction of proteins involved in cell-survival pathways such as HSP70, HSP40, p21, GADD45beta, Ier3, and Nf-kappaB. Moreover, increased expression of three of these factors after noise was confirmed at the protein level. Drastically enhanced HSP70, GADD45beta, and p21 immunostaining were detected 6 h after the noise exposure in subsets of cells of the lateral wall, spiral limbus, and organ of Corti as well as in cochlear nerve fibers. Upregulation of these proteins after noise exposure likely contributes to the prevalence of survival cellular pathways and thus to the resistance to NIHL that is characteristic of the 129X1/SvJ mice.
Publication Title
Noise-induced changes in gene expression in the cochleae of mice differing in their susceptibility to noise damage.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- NextSeq 500
Description
Podocytes are highly specialised cells within the glomeruli of the kidney that maintain the filtration barrier by forming interdigitating foot processes and slit-diaphragms. Disruption to these features result in proteinuria and glomerulosclerosis. Studies into podocyte biology and disease have previously relied on conditionally immortalised cell lines due to the non- proliferative nature of this cell type. Here we describe an advanced model to study both podocyte and glomerular biology using isolated glomeruli from kidney organoids derived from human pluripotent stem cells. Overall design: Gene expression profiling of day three 17, 21 and 26 day kidney organoid derived glomeruli respectively with heterzygous genotype for BFP tagged MAFB; gene expression profiling of three day 25 kidney organoid derived glomeruli; gene expression profiling of three organoid-derived podocytes grown out for 3 days from day 25 kidney organoid derived glomeruli.
Publication Title
3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Imbalances in glucose and energy homeostasis are at the core of the worldwide epidemic of obesity and diabetes. Here, we illustrate an important role of the TGF-beta/Smad3 signaling pathway in regulating glucose and energy homeostasis. Smad3 deficient mice are protected from diet-induced obesity and diabetes. Interestingly, the metabolic protection is accompanied by Smad3-/- white adipose tissue acquiring the bioenergetic and gene expression profile of brown fat/skeletal muscle. Smad3-/- adipocytes demonstrate a marked increase in mitochondrial biogenesis, with a corresponding increase in basal respiration, and Smad3 acts as a repressor of PGC-alpha1 expression. We observe significant correlation between TGF-beta1 levels and adiposity in rodents and humans. Further, systemic blockade of TGF-beta1 signaling protects mice from obesity, diabetes and hepatic steatosis. Together, these results demonstrate that TGF-beta signaling regulates glucose tolerance and energy homeostasis and suggest that modulation of TGF-beta1 activity might be an effective treatment strategy for obesity and diabetes.
Publication Title
Protection from obesity and diabetes by blockade of TGF-β/Smad3 signaling.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Natural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy.
Publication Title
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Saccharomyces cerevisiae
- 19 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The SCH9 null strain has smaller cell size, grows at a slower rate and survives three times longer than wide-type yeast.
Publication Title
Comparative analyses of time-course gene expression profiles of the long-lived sch9Delta mutant.
Sample Metadata Fields
Age
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The three yeast mutants sch9, ras2, tor1 show extended chronological life span up to three folds.
Publication Title
Significant and systematic expression differentiation in long-lived yeast strains.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We conducted a genome-wide expression analysis of wild-type males using three cell populations isolated from mitotic, meiotic and post-meiotic phases of spermatogenesis in Drosophila melanogaster. Our approach was to directly isolate testis regions enriched with RNAs from each of the three specific germline phases.
Publication Title
Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
TGFbeta induces VSMC gene expression in human coronary artery smooth muscle cell (HCASM) Overall design: Subconfluent human coronary artery smooth muscle cells (HCASM) were starved overnight followed by TGFbeta treatment for 24 hours. RNA was then extracted for deep-sequencing.
Publication Title
Transforming growth factor β1 suppresses proinflammatory gene program independent of its regulation on vascular smooth muscle differentiation and autophagy.
Sample Metadata Fields
Treatment, Subject
View Samples