The ability to assign expression patterns to individual cell types that constitute a tissue is a major challenge in RNA expression analysis. This especially applies to brain given the plethora of different cells coexisting in that tissue. Here, we derived cell-type specific transcriptome signatures from existing single cell RNA data and integrated these signatures with a newly generated dataset of expression (bulk RNA-seq) of the postnatal developing hippocampus. This integrated analysis allowed us to provide a comprehensive and unbiased prediction of the differentiation drivers for 10 different hippocampal cell types and describe how the different cell types interact to support crucial developmental stages. Our integrated analysis provides a reliable resource of predicted differentiation drivers and insight into the multifaceted aspects of the cells in hippocampus during development. Overall design: 21 RNA-seq samples. For the stages E15, P1, P7, P15, and P30, there are respectively 3, 4, 3, 3, and 6 RNA-seq biological replica (total 19). One RNA-seq sample has two technical replica.
Integrated transcriptional analysis unveils the dynamics of cellular differentiation in the developing mouse hippocampus.
Specimen part, Cell line, Subject
View SamplesThe X-linked DDX3X gene encodes an ATP-dependent DEAD-box RNA helicase frequently altered in various human cancers including melanomas. Despite its important roles in translation and splicing, how DDX3X dysfunction specifically rewires gene expression in melanoma remains completely unknown. Here we uncover a DDX3X-driven post-transcriptional program that dictates melanoma phenotype and poor disease prognosis. Through an unbiased analysis of translating ribosomes we identified the microphtalmia-associated transcription factor, MITF, as a key DDX3X translational target that directs a proliferative-to-metastatic phenotypic switch in melanoma cells. Mechanistically, DDX3X controls MITF mRNA translation via an internal ribosome entry site (IRES) embedded within the 5' untranslated region. Through this exquisite translation-based regulatory mechanism, DDX3X steers MITF protein levels dictating melanoma metastatic potential in vivo and response to targeted therapy. Together these findings unravel a post-transcriptional layer of gene regulation that may provide a unique therapeutic vulnerability in aggressive male melanomas. Overall design: We sequenced transcripts associated with translationally active ribosomes (polysomes) isolated by sucrose gradient fractionation from DDX3X and control siRNA-transduced HT144 cells. Experiments were performed in duplicates.
The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma.
Specimen part, Cell line, Subject
View SamplesCells lacking Rb1 are deficient in differentiation. Loss of Kdm5a rescues myogenic differentiation, as judged by appearance of morphologically normal myotubes that display expression of late markers of differentiation. In order to better understand how Kdm5a loss rescues differentiation, we induced mouse embryonic fibroblasts (MEFs) of different genotypes to undergo myogenic differentiation and analyzed gene expression changes in wild-type, Kdm5a-/-, Rb1-/- and Kdm5a-/-; Rb1-/- cells. Rb1-/- cells stained single nucleated, did not exhibit morphological changes and increased expression of the myogenic marker MYHC. Except for Rb1-/- cells, all other cells were undergoing successful convertion into aligned multinucleated myotubes and were MYHC-positive. We obtained purified populations of myotubes for the wild-type and Kdm5a-/-; Rb1-/- cells. Overall design: RNA-seq analysis of gene expression in Rb1 or Kdm5a deficient MEFs that were induced for myogenic differentiation.
Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells.
No sample metadata fields
View SamplesApoptosis is an important process to eliminate cells from tissue which have incurred irreparable DNA damage. While dE2F1/dDP complexes respond to such damage by transcriptionally activating apoptotic genes, previous data suggests that activation of the previously characterized apoptotic target genes of dE2F1/dDP alone may not be the only gene regulation important for gamma irradiation-induced apoptosis. Here we report that following irradiation in dDP mutant 3rd instar larval eye imaginal discs, many genes important for oxidative phosphorylation are down-regulated, which are not down-regulated following irradiation in wild type eye discs.
Loss of dE2F compromises mitochondrial function.
Specimen part, Treatment
View SamplesEarly-passage (<10 passages) cultures of melanoma cells from metastatic lymph node lesions and normal adult melanocytes explanted in parallel from the adjacent, non-involved skin of 5 patients were compared by cDNA arrays. Differences between normal and neoplastic counterparts were then assessed upon adjustment for individual factors.
A melanoma immune response signature including Human Leukocyte Antigen-E.
Sex, Specimen part
View SamplesRBP2 is downstream of pRB pathway
Genome-wide analysis of the H3K4 histone demethylase RBP2 reveals a transcriptional program controlling differentiation.
No sample metadata fields
View SamplesAntitoxins are becoming recognized as proteins that regulate more than their own synthesis; for example, we found previously that antitoxin MqsA represses the gene encoding the stationary phase sigma factor RpoS. Here, we investigated the physiological role of antitoxin DinJ of the DinJ/YafQ toxin/antitoxin system and found DinJ also affects the general stress response by decreasing RpoS levels. Corroborating the reduced RpoS levels upon producing DinJ, catalase activity, cell adhesins, and cyclic diguanylate decreased while swimming increased. Using a transcriptome search and DNA-binding assays, we determined that the mechanism by which DinJ reduces RpoS is by repressing cspE which encodes cold-shock protein CspE that inhibits translation of rpoS mRNA. Hence, DinJ influences the general stress response indirectly by regulating cspE.
Antitoxin DinJ influences the general stress response through transcript stabilizer CspE.
Time
View SamplesWe have used the citrus GeneChip array (GPL5731) to survey the transcription profiles of sweet orange in response to the bacterial pathogens Xanthomonas axonopodis pv. citri (Xac) and Xanthomonas axonopodis pv. aurantifolii (Xaa). Xac is the causal agent of the citrus canker disease on a wide range of citrus species, including sweet oranges (Citrus sinensis). On the other hand, Xaa is pathogenic to Mexican lime (Citrus aurantifolia) only, and in sweet orange it triggers a defense response. In order to identify the genes induced during the defense response (Xaa-responsive genes) or citrus canker development (Xac-responsive genes), we conducted microarrays hybridization experiments at 6 and 48 hours after bacterial infiltration (habi). The analysis revealed that genes commonly modulated by Xac and Xaa are associated with basal defenses normally triggered by pathogen-associated molecular patterns, including those involved in reactive oxygen species production and lignification. Significantly, Xac-infected leaves showed considerable changes in the transcriptional profiles of defense-, cell wall-, vesicle trafficking- and cell growth-related genes between 6 and 48 habi. This is consistent with the notion that Xac suppresses host defenses near the beginning of the infection and simultaneously changes the physiological status of the host to promote cell enlargement and division. Finally, Xaa triggered a MAP kinase signaling pathway involving WRKY and ethylene-responsive transcriptional factors known to activate downstream defense genes.
Transcriptional analysis of the sweet orange interaction with the citrus canker pathogens Xanthomonas axonopodis pv. citri and Xanthomonas axonopodis pv. aurantifolii.
No sample metadata fields
View SamplesPersister cells are a sub-population of all bacterial cultures which exhibit a non-inheritable, multi-drug tolerance when subjected to lethal antibiotic challenge. These persisters arise as a result of metabolic dormancy, and can resume growth subsequent to antibiotic challenge, leading to recalcitrance of bacterial infections.
Phosphodiesterase DosP increases persistence by reducing cAMP which reduces the signal indole.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Cell line, Treatment, Time
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