Regeneration 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 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 SamplesDifferent mutations in the gene encoding humans IGF-I cause intrauterine growth retardation, postnatal growth failure, microcephaly, mental retardation, bilateral sensorineural deafness and multiple dysmorphic features. Insight into the role of IGFs in inner ear cochlear ganglion neurogenesis has come from the study of genetically modified mice. Postnatal cochlear development is severely impaired in mice Igf1-/-, which develop smaller cochlea and cochlear ganglia, an immature tectorial membrane and they display a significant decrease in the number and size of auditory neurons.
RNA microarray analysis in prenatal mouse cochlea reveals novel IGF-I target genes: implication of MEF2 and FOXM1 transcription factors.
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View SamplesWe identified a novel homozygous 15q13.3 microdeletion in a young boy with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness (CSNB), congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype. We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions.
Genome-wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome.
Cell line
View Samplesdetermination of gene regulation by sterol and sphingolipid composition
Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology.
Sex
View SamplesRNA sequencing of human dermal fibroblasts from CAID patients passage 8 and passage 14 Overall design: RNA sequencing was perfomed on 3 wild type controls and 3 CAID patients fibroblast cell lines at cell passages 8 and 14. Sequencing was performed on Illumina Hiseq4000, 8 samples/lanes, paired-end.
Molecular Signature of CAID Syndrome: Noncanonical Roles of SGO1 in Regulation of TGF-β Signaling and Epigenomics.
Specimen part, Subject
View SamplesWe used microarrays to compare the global programme of gene expression in HTLV-positive, ATL-derived and HTLV-positive in vitro-transformed cell lines with that of uninfected primary CD4 T cells.
Elevated cyclic AMP levels in T lymphocytes transformed by human T-cell lymphotropic virus type 1.
Specimen part
View SamplesThe goal of the study was to compare transcriptome changes in HeLa cells after infection with recombinant Thogoto virus (wild-type, ML deletioin mutant or ML SW mutant not able to interact wiith TFIIB. While wild-type virus is able to inhibit inflammatory genes, ML deletion mutant and TFIIB-non-interacting mutant lose this effect on gene transcription. Overall design: Examination of transcriptome changes in HeLa cells under steady state or after THOV infection using Illumina HiSeq.
Viral targeting of TFIIB impairs de novo polymerase II recruitment and affects antiviral immunity.
Cell line, Subject
View SamplesProjection-dependent ribosome profling from mouse mPFC.
Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.
Specimen part
View SamplesAnalysis of primary bovine aortic endothelial cells treated for 24 hours with TGF-beta 1 5 ng/ml. TGF-beta 1 has been shown to induce endothelial-to-mesenchymal transition (EndoMT) and to be implicated in differentiation of endothelial cells into smooth muscle-like cells as occurred in vascular neointimal formation.
LOXL4 is induced by transforming growth factor β1 through Smad and JunB/Fra2 and contributes to vascular matrix remodeling.
Specimen part
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