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Gene expression study of developing mammalian vestibular organ of wild type and Insulin-Like Growth Factor I deficient mice using Affymetrix whole transcript arrays

ABSTRACT: Insulin like growth factor 1 (IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system. In this study we have compared the whole transcriptome of the vestibular organ from wild type and Igf1-/- mice at different developmental times. RNA was prepared from E18.5, P15 and P90 vestibular organs of Igf1-/- and Igf1+/+ mice and the transcriptome analyzed in triplicates using Affymetrix® Mouse Gene 1.1 ST Array Plates.

ORGANISM(S): Mus musculus

SUBMITTER: Marta Milo

PROVIDER: E-GEOD-65202 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression study of developing mammalian vestibular organ of wild type and Insulin-Like Growth Factor I deficient mice using Affymetrix whole transcript arrays

Project description:Insulin like growth factor 1 (IGF-1) has a central role in mammalian hearing and hearing loss. The auditory and vestibular systems form the inner ear and have a common developmental origin. During chicken early development IGF-1 modulates neurogenesis of the cochleovestibular ganglion but no further studies have been conducted to explore the potential role of IGF-1 in the vestibular system. In this study we have compared the whole transcriptome of the vestibular organ from wild type and Igf1-/- mice at different developmental times.

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Transcription profiling of mouse Igf1 null mutant

Project description:Different 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. We used microarrays to define the genetic signatures of Igf-1 +/+ and Igf-1-/- mouse cochea and identify the differentially expressed genes. Experiment Overall Design: Cochleae from two E18.5 were isolated from both Igf-1+/+ wild type and Igf-1-/- null mice and pooled to obtain RNA. Heterozygous male and female with a genetic background C57BL/6J were mated to obtain embryos 18.5 days post coitus (E18.5). Three independent pools were used. Cochlear tissues included the otic capsule but not vestibular tissues.

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Transcription profiling of mouse Igf-1 -/- and Igf-1+/+ cochleas

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CXCL12 and IGF1 select for cancer cell populations with enhanced bone metastasis ability

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Project description:Skeletal muscle mediates the beneficial effects of exercise, thereby improving insulin sensitivity and reducing the risk for type 2 diabetes. Current skeletal-muscle-models in vitro are incapable of fully recapitulating its physiological functions especially regarding exercise. Supplementation of IGF1, a growth factor secreted by myofibers in vivo, might help to overcome these limitations. Primary human CD56-positive myoblasts were differentiated into myotubes in the presence/absence of IGF1 in serum-free medium for 10 days. Daily collected samples were analyzed by proteomics, qRT-PCR and myotube contractibility via electrical-pulse-stimulation (EPS). Mitochondrial respiration and glucose uptake were measured. IGF1-supported differentiation formed thicker multinucleated myotubes showing physiological contraction upon EPS following day 6 while myotubes without IGF1 were almost incapable of contraction. IGF1-treatment upregulated particularly muscle-specific proteins that contribute to myofibril and sarcomere assembly, striated muscle contraction, and ATP production. Elevated PPARGC1A, MYH7 and reduced MYH1/2 suggest a switch towards a more oxidative phenotype in line with elevated mitochondrial respiration. IGF1-treatment also upregulated expression of GLUT4 and increased insulin-dependent glucose uptake. To conclude, utilizing IGF1, we engineered human myotubes that recapitulate the physiological traits of skeletal muscle in vivo vastly superior to established protocols. This novel model enables investigation of exercise on a molecular level, drug screening and interorgan-crosstalk by transfer to organ-on-chip.

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Polysome-associated mRNA profiling of cancer cells in response to CXCL12 and IGF1

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2013-11-01 | E-GEOD-43296 | biostudies-arrayexpress

Transcriptional analysis of apoptotic cerebellar granule neurons following rescue by Gip, Sp, Pacap and Igf1

Project description:Primary cultures of Cerebellar Granule Neurons (CGNs) have been extensively utilized to examine the signal transduction mechanisms underlying neuronal apoptosis. We conducted whole-genome expression profiling to decipher the transcriptional program controlling the apoptotic/survival switch in cerebellar granule neurons (CGNs) following the induction of apoptosis by serum and potassium deprivation and their rescue by gastric inhibitory polypeptide (Gip), substance p (Sp), insulin-like growth factor-1 (Igf1) or pituitary adenylyl cyclase-activating polypeptide (Pacap). Our results reveal the transcriptional changes intersecting neuronal apoptosis and survival and form the basis for further functional analyses and pharmacological exploitation to identify neuroprotective drugs. After six days âin vitroâ (DIV), extracellular KCl of CGNs was shifted from 25 to 5 mM for neuronal apoptotic death induction. After two washes with serum-free BME containing 5 mM KCl, neurons were incubated with the same medium for 6 h (K5), while control neurons were incubated with serum free medium supplemented with 25 mM KCl (K25). K5 neurons were also treated with a maximal effective dose of Gip, Sp, Igf1 and Pacap. Four biological replicates (derived from the same litter) for each of the experimental conditions (K25, K5, K5 + Gip; K25, K5, K5 + Sp; K25, K5, K5 + Igf1; K25, K5, K5 + Pacap) were analyzed.

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