Targets of Retinoic Acid (RA) and 3,4-didehydroretinoic acid (ddRA) were identified in primary human epidermal keratinocytes grown in the presence of atRA or ddRA for 4 and 24 hours.
The effect of two endogenous retinoids on the mRNA expression profile in human primary keratinocytes, focusing on genes causing autosomal recessive congenital ichthyosis.
Treatment
View SamplesWe analyzed small RNAs from three mammalian species, and found that in all these species piRNA-directed targeting is accompanied by the generation of short sequences that have a very precisely defined length and a specific spatial relationship with the guide piRNAs. Overall design: small RNA-seq of testes lysate (beta-eliminated)
Conserved generation of short products at piRNA loci.
No sample metadata fields
View SamplesA key requisite for the success of a dendritic cell (DC)-based vaccine in treating malignancies is the capacity of the DCs to attract immune effector cells for further interaction and activation, considering crosstalk with DCs is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC therapy. In this paper we examine if the so-called interleukin (IL)-15 DC vaccine provides a favorable chemokine milieu for recruiting T cells, natural killer (NK) cells and gamma delta () T cells, in comparison with the IL-4 DCs used routinely for clinical studies, as well as the underlying mechanisms of immune cell attraction by IL-15 DCs. Chemokine signaling is studied both at the RNA level, using microarray data of mature DCs, and functional level, by means of a transwell chemotaxis assay. Important to note, the classic IL-4 DC vaccine falls short to attract the required immune effector lymphocytes, whereas the IL-15 DCs provide a favorable chemokine milieu for recruiting all cytolytic effector cells. The elevated secretion of the chemokine (C-C motif) ligand 4 (CCL4), also known as macrophage inflammatory protein-1 (MIP-1), by IL-15 DCs underlies the enhanced migratory responsiveness of T cells, NK cells and T cells. Namely, neutralizing its receptor CCR5 resulted in a significant drop in migration of the aforementioned effector cells towards IL-15 DCs. These findings should be kept in mind in the design of future DC-based cancer vaccines.
Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells.
Specimen part, Subject
View SamplesDespite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-wide expression analysis confirmed that treatments promoting neuronal reprogramming elicit an anti-oxidative stress response. Importantly, coexpression of Bcl-2 and anti-oxidative treatments lead to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury in vivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type, in vitro and in vivo.
Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming.
Sex, Specimen part
View SamplesMicroarray analysis of gene expression after transverse aortic constriction in mice: comparison of TAC vs. sham group at 48 hours, 10 days, and 3 weeks.
Microarray analysis of gene expression after transverse aortic constriction in mice.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Specimen part
View SamplesWe used microarrays to detail the differentail gene expression between intestinal Lgr5(hi) stem cells and differentiated cells
DOT1L-mediated H3K79 methylation in chromatin is dispensable for Wnt pathway-specific and other intestinal epithelial functions.
Specimen part
View SamplesTuberous sclerosis complex (TSC) is a rare genetic disease characterized by mTOR hyperfunction induced benign tumor growths in multiple organs and neurological symptoms. Because the molecular pathology is highly complex and the etiology poorly understood we employed a defined human neuronal model with a single mTOR activating mutation to dissect the disease-relevant molecular responses driving the neuropathology. TSC2 deficient neural stem cells showed severely reduced neuronal functional maturation and characteristics of astrogliosis instead. Accordingly, transcriptome analysis uncovered an inflammatory response and increased metabolic activity, while ribosome profiling revealed excessive translation of ribosomal transcripts and higher synthesis rates of angiogenic growth factors. Treatment with mTOR inhibitors corrected translational alterations but not transcriptional dysfunction. These results extend our understanding of the molecular pathophysiology of TSC brain lesions, and suggest phenotype-tailored pharmacological treatment strategies. Overall design: Two TSC+/- cell lines and two TSC-/- cell lines were independently generated from wild-type human embryonic stem cells by genome editting with zinc finger nucleases. Two cell lines were handled in the same way but without any known human gene editted and they are used as negative controls. Two independent biological replicates of each of the six cell lines are profiled with ribosome profiling technique.
Genomic analysis of the molecular neuropathology of tuberous sclerosis using a human stem cell model.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Specimen part
View SamplesDespite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency or developmentally related gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarify the temporal order through which somatic identity is reset during reprogramming.
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Specimen part
View Samples