We purified Atoh1-GFP positive hair cells from organotypic cultures of P1 cochlea 3 hours after 0.5mM gentamicin treatment and performed RNA sequencing to profile the early transcriptional response of hair cells to aminoglycoside antibiotics. Overall design: Levels of mRNA in gentamicin-treated hair cells (three replicates) were compared to untreated hair cells (three replicates). GFP negative, non-hair cells populations from treated organs were compared to those from untreated organs (three replicates for each condition).
Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis in sensory hair cells in the mouse inner ear.
No sample metadata fields
View SamplesPsoriasis is a chronic inflammatory skin disease related to immune, whose complexity of molecular mechanisms is still not fully clear. RNA sequencing has been widely applied in various fields including biological medicine. According to the bioinformatics analysis of differential genes, biomarkers and drug targets have been discovered for the diagnosis and treatment of diseases. Besides, the pathological mechanisms of disease and functions of gene can be evaluated. In the present study, we report the application of RNA sequencing in skin tissues from psoriatic and healthy persons. By obtaining 2139 differential expressed genes (DEGs), 208 significantly differential GO terms and 44 significantly differential pathways were generated. We found that the functions of DEGs were mainly related to cell cycle, inflammatory, virus, immune response and metabolic process.The major pathways included cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway, cell cycle, metabolic pathways, ribosome, peroxisome, steroid biosynthesis and biosynthesis of unsaturated fatty acids. Furthermore, co-expression network was constructed to identify core genes and relations between genes. we considered genes with high values of degree and k-core difference in the co-expression network as core genes, such as IFNG, IL26, TLR3, PRKCQ, TLR4, CD274, CDK1 and IL17A. We chose CD274, an important immune checkpoint, to evaluate its regulatory mechanisms. Candidate genes related to CD274 were evaluated by the co-expression network analysis, and the relations between CD274 and candidate genes were validated in epidermal keratinocytes. Finally, IFNG and CDK1 inhibitor (indirubin) were found increasing the expression levels of CD274. In addition, indirubin was confirmed to attenuate mouse psoriasis-like skin lesion with the mechanisms related to CD274. In conclusion, this study provides us a comprehensive transcriptome analysis method on psoriasis to identify core genes and explore the important regulatory functions of genes. Overall design: Nine normal skins from healthy volunteers and 18 lesional skins from patients with psoriasis vulgaris were obtained for RNA sequencing
Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induced p53 loss in mouse luminal cells causes clonal expansion and development of mammary tumours.
Sex, Specimen part
View SamplesKeratinocytes are the major constituent of epithelial cells at mucosal surfaces and skin, which cover organs, internal cavities and the body. Traditionally, keratinocytes have been considered as an inert component of the multilayered epithelium to protect the subepithelial compartments from the pathogenic microorganisms, toxic stimuli and physical trauma. However, accumulated researches of the airway, gastrointestinal tract and skin have demonstrated that keratinocytes function in the development of the immune system, promotion of pathologic inflammation and even impose diverse decisions on immune cells.
Genome-wide analysis reveals the active roles of keratinocytes in oral mucosal adaptive immune response.
Specimen part, Time
View SamplesWe previously reported that Def (Digestive-organ expansion factor) was a pan-endodermal enriched factor that is essential for the growth of digestive organs in zebrafish using a def mutant line hi429 as model (Chen et al., 2005). To further elucidate Def function, we generated a Def over-expressed zebrafish line, namely Tg (fabp10a:def)-I, in which def expression was under the control of a liver-specific promoter fabp10a.
Def functions as a cell autonomous factor in organogenesis of digestive organs in zebrafish.
Sex, Specimen part
View SamplesHematopoietic cells represent an attractive starting cell type for induced pluripotent stem (iPS) cells induction, yet the molecular mechanisms in hematopoietic reprogramming are poorly defined. In this study, we showed that long-term hematopoietic stem cells are more amenable for iPS cells induction among several hematopoietic stem and progenitor cell (HSPC) populations, and that this is accompanied by an earlier induction of the transcriptional program that is involved in the promotion of macromolecule metabolism and cell proliferation. Notably, we identified multiple signaling pathways that exhibited distinct expression patterns in HSPCs compared to that of fibroblasts, which is the most commonly used model for probing the somatic reprogramming process. We further experimentally confirmed the differential requirements of the Wnt/ß-catenin and transforming growth factor-beta (TGF-ß) signaling pathways in these two cell types. These data demonstrate that hematopoietic cells have a cell-type specific transcriptional program and possess unique signaling requirements in the early phase of reprogramming. Overall design: Examine the differential global gene expression among different hematopietic cells in reprogramming. LT-HSC, ST-HSC, MP and fibroblasts were used in this study. Doxcycline addition could induce expression of oct4, sox2, klf4 and c-myc, consequently reprogramming these cells into iPS cells. Hematopietic cells cultured with doxcycline for 0, 2, 4 days were sampled, and samples at the same timepoint without doxcycline were also taken to exclude vast gene expression change in hematopoietic cell in-vitro culture. Fibroblast samples induced by doxcycline for 0, 2, 4 days were also introduced to provide comparism between lineages.
Cell type-specific expression profile and signaling requirements in early hematopoietic reprogramming.
No sample metadata fields
View SamplesTo understand the transcriptional program controlled by RGA, we took advantage of a functional steroid-inducible RGA proteins system in combination with microarray analysis to identify RGA target genes.
Global identification of DELLA target genes during Arabidopsis flower development.
No sample metadata fields
View SamplesHere, we performed single nuclear RNA-seq (snRNA-seq) of control and Pitx2 deficient cardiac tissue 3 weeks post myocardial infarction. Next, unsupervised graph-based clustering of the combined snRNA-Seq data set mapped to both introns and exons, comprising 7848 cells. Overall, we identified nine transcriptionally distinct clusters representing all the major cardiac cell types, including cardiac fibroblasts (FB), cardiomyocytes (CM), endothelial cells (EC), vascular smooth muscle cells (SMC), macrophages (Mf), epicardial cells (EpiC), endocardial cells (EndoC), lymphatic endothelial cells (LEC), and mural cells or pericytes (PeC). Moreover, two distinct populations of fibroblasts, designated FB-1 and FB-2, were also identified. Overall design: Cardiac tissue dissociated, nuclei were isolated via density gradient centrifugation, and then ran through the 10X Chromium device to generate snRNA-seq libraries that were sequenced on an Illumina NextSeq 500.
<i>Pitx2</i> maintains mitochondrial function during regeneration to prevent myocardial fat deposition.
Specimen part, Subject, Time
View SamplesOncogenic Ras induces epidermal cell growth arrest. Induction of the JNK/Ap1 signaling cascade by expression of MKK7 overcomes Ras-induced cell growth arrest in a manner dependent on AP1 fucntion.
Tumor necrosis factor receptor 1/c-Jun-NH2-kinase signaling promotes human neoplasia.
No sample metadata fields
View SamplesRett syndrome is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here we report a test of the hypothesis of shared pathophysiology of Rett syndrome and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein synthesis-dependent synaptic plasticity is similarly altered in area CA1 of Mecp2 KO mice. CA1 pyramidal cell-type-specific, genome-wide profiling of ribosome-bound mRNAs was performed in wild-type and Mecp2 KO hippocampal CA1 neurons to reveal the MeCP2-regulated 'translatome'. We found significant overlap between ribosome-bound transcripts overexpressed in the Mecp2 KO and FMRP mRNA targets. These tended to encode long genes that are functionally related to either cytoskeleton organization or the development of neuronal connectivity. In the Fmr1 KO mouse, chronic treatment with mGluR5 negative allosteric modulators (NAMs) has been shown to ameliorate many mutant phenotypes by correcting excessive protein synthesis. In the Mecp2 KO mice we found that mGluR5 NAM treatment significantly reduces the level of overexpressed ribosome-associated transcripts, particularly those that are also FMRP targets. Some Rett phenotypes were also ameliorated by treatment, most notably hippocampal cell size and life span. Together, these results suggest a potential mechanistic link between MeCP2-mediated transcription regulation and mGluR5/FMRP-mediated protein translation regulation through co-regulation of a subset of genes relevant to synaptic functions. Overall design: TRAP-seq analysis of the effect of negative modulator of mGluR5 on the CA1 neurons (marked by Cck-EGFP-L10a) of a mouse model of Rett syndrome
Negative Allosteric Modulation of mGluR5 Partially Corrects Pathophysiology in a Mouse Model of Rett Syndrome.
Specimen part, Cell line, Treatment, Subject
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