Microarray analysis of dithranol-treated psoriasis lesions before, during and after therapy
Dithranol targets keratinocytes, their crosstalk with neutrophils and inhibits the IL-36 inflammatory loop in psoriasis.
Time
View SamplesThe discovery of mammalian cardiac progenitor cells has suggested that the heart consists of not only terminally differentiated beating cardiomyocytes, but also a population of self-renewing stem cells with the potential to generate new cardiomyocytes (Anderson, Self et al. 2007; Bearzi, Rota et al. 2007; Wu, Chien et al. 2008). A consequence of longevity is continual exposure to environmental and xenobiotic stresses, and recent literature suggests that hematopoietic stem cell pools tightly control cell health through upregulation of the integrated stress response and consequent cellular mechanisms such as apoptosis. However, whether or not this biological response is conserved in progenitor cells for later lineages of tissue specific stem cells is not well understood. Using human induced pluripotent stem cells (iPSC) of both cardiac progenitor and mature cardiomyocyte lineages, we found that the integrated stress response was upregulated in the iPSC cardiac progenitors leading to an increased sensitivity for apoptosis relative to the mature cardiomyocytes. Of interest, C/EBP homologous protein (CHOP) signaling plays a mechanistic role in the cell death phenotype observed in iPSC progenitors, by which depletion of CHOP prevents cell death following cellular stress by thapsigargin exposure. Our studies suggest that the integrated stress response plays a unique role in maintaining iPSC cardiac progenitor cellular integrity by removing unhealthy cells via apoptosis following environmental and xenobiotic stresses, thus preventing differentiation and self-renewal of damaged cells.
The Integrated Stress Response Regulates Cell Health of Cardiac Progenitors.
Specimen part, Treatment
View SamplesRegeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny. Immuno-localization revealed high expression levels of Igf1r (Insulin-like Growth Factor 1 Receptor) in lung epithelial cells, alveolar macrophages and smooth muscle. To further understand the role of Igf1r in pulmonary homeostasis, two distinct lung epithelial-specific Igf1r mutant mice were generated and studied. The lack of Igf1r disturbed airway epithelial differentiation in adult mice revealed enhanced proliferation and altered morphology in distal airway club cells. During recovery after naphthalene-induced club cell injury, the kinetics of terminal bronchiolar epithelium regeneration was hindered in Igf1r mutants, revealing increased proliferation and delayed differentiation of club and ciliated cells. Amid airway restoration, lungs of Igf1r deficient mice showed increased levels of Igf1, Insr, Igfbp3 and epithelial precursor markers, reduced amounts of Scgb1a1 protein, and alterations in IGF signaling mediators. These results support the role of Igf1r in controlling the kinetics of cell proliferation and differentiation during pulmonary airway epithelial regeneration after injury. Overall design: Lung mRNA profiles of 3 months-old Igf1rfl/fl normal/control transgenic mice were generated by deep sequencing using Illumina GAIIx. ------------------------------------------- Submitter states "we use data on the absolute transcription levels (FPKM) of same IGF system genes on the adult "normal" mouse lung to compare them with those reported in the human adult lung (expressed in both as FPKM) (http://www.proteinatlas.org/)".
Involvement of Igf1r in Bronchiolar Epithelial Regeneration: Role during Repair Kinetics after Selective Club Cell Ablation.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.
Specimen part
View SamplesGenome-wide transcriptional profiling of purified telomerase deficient (Terc-/-) and WT LSCs was performed in order to gain insights into the mechanisms underlying the susceptibilities of Terc-/- LSCs in vivo.
Telomerase inhibition effectively targets mouse and human AML stem cells and delays relapse following chemotherapy.
Specimen part
View SamplesDevelopmental programming is the concept that environmental factors, particularly during foetal life, can alter development, metabolism and physiology of an organism and this can have consequences later in life. There is growing interest in developmental programming in livestock species, particularly effects of maternal pregnancy nutrition, which is easy to manipulate. Recent research, using a sheep model, has shown that milk production in ewe offspring may be susceptible to maternal nutritional programming, such that over nutrition (ad libitum) of the pregnant dam, compared with maintenance nutrition, may impair their first lactation performance and result in the weaning of lighter lambs. RNA-seq was performed to identify gene expression differences as a result of maternal nutrition in ewe offspring during their first parity. Samples were collected in late pregnancy and during lactation, allowing us to examine gene expression changes during maturation of the ovine mammary gland. Overall design: Three biological replicates were sequenced for each of the treatment conditions (maternal nutrition: sub-maintenance, maintenance, and ad libitum) and time points (late pregnancy and lactation). Each biological replicate consisted of RNA from multiple individuals (late pregnancy n=3, lactation n=2).
Functional development of the adult ovine mammary gland--insights from gene expression profiling.
Specimen part, Subject
View SamplesMicroRNAs (miRNAs) are short noncoding RNA molecules regulating the expression of mRNAs. Target identification of miRNAs is computationally difficult due to the relatively low homology between miRNAs and their targets. We present here an experimental approach to target identification where the cartilage-specific miR-140 was overexpressed and silenced in cells it is normally expressed in separate experiments. Expression of mRNAs was profiled in both experiments and the intersection of mRNAs repressed by miR-140 overexpression and derepressed by silencing of miR-140 was identified. The intersection contained only 49 genes, although both treatments affected the accumulation of hundreds of mRNAs. These 49 genes showed a very strong enrichment for the miR-140 seed sequence implying that the approach is efficient and specific. 21 of these 49 genes were predicted to be direct targets based on the presence of the seed sequence. Interestingly, none of these were predicted by the published target prediction methods we used. One of the potential target mRNAs, Cxcl12, was experimentally validated by Northern blot analysis and a luciferase reporter assay.
Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140.
No sample metadata fields
View SamplesInsight into the role of Insulin-like Growth Factor (IGF) in development of lungs has come from the study of genetically modified mice. IGF1 is a key factor during lung development. IGF1 deficiency in the neonatal mouse causes respiratory failure collapsed alveoli and altered alveolar septa. To further characterize IGF1 function during lung development we analyzed Igf1-/- mouse prenatal lungs in a C57Bl/6 genetic background. Mutant lungs showed disproportional hypoplasia, disorganized extracellular matrix and dilated alveolar capillaries. IGF1 target genes during lung maturation were identified by analyzing RNA differential expression in Igf1-/- lungs using microarrays.
Transcriptome analysis in prenatal IGF1-deficient mice identifies molecular pathways and target genes involved in distal lung differentiation.
Specimen part
View SamplesComparison of expression profile of Ewing''s sarcoma with cell of origin, mesenchymal stem cells with the goal of identifying novel therapeutic targets. Overall design: 3 Ewing''s cell lines compared to 2 MSC cell lines
Exploring the surfaceome of Ewing sarcoma identifies a new and unique therapeutic target.
No sample metadata fields
View SamplesGene-expression microarray datasets generated as part of the Immunological Genome Project (ImmGen). Primary cells from multiple immune lineages are isolated ex-vivo, primarily from young adult B6 male mice, and double-sorted to >99% purity. RNA is extracted from cells in a centralized manner, amplified and hybridized to Affymetrix 1.0 ST MuGene arrays. Protocols are rigorously standardized for all sorting and RNA preparation. Data is released monthly in batches of cell populations.
Transcriptomes of the B and T lineages compared by multiplatform microarray profiling.
Sex, Age
View Samples