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Identification of transcript dysregulation in patients with Autism Spectrum Disorders

ABSTRACT: In order to unveil the molecular mechanisms at play during the development of autistic brains, we studied cells that are representative of the very early stages of ontogenesis, namely stem cells. We used nasal olfactory stem cells that are readily accessible and can be biopsied safely. We recruited a relatively homogeneous cohort of nine adults with severe autism and low to very low developmental disabilities, and included two more adults with either Asperger syndrome or high-functioning autism, to enlarge the spectrum. The cohort was then paired with 11 age- and gender-matched control individuals. Stem cells were purified, banked and used for a transcriptomic study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE63524 | GEO | 2014/11/22

SECONDARY ACCESSION(S): PRJNA268178

REPOSITORIES: GEO

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Identification of transcript dysregulation in patients with Autism Spectrum Disorders

Project description:In order to unveil the molecular mechanisms at play during the development of autistic brains, we studied cells that are representative of the very early stages of ontogenesis, namely stem cells. We used nasal olfactory stem cells that are readily accessible and can be biopsied safely. We recruited a relatively homogeneous cohort of nine adults with severe autism and low to very low developmental disabilities, and included two more adults with either Asperger syndrome or high-functioning autism, to enlarge the spectrum. The cohort was then paired with 11 age- and gender-matched control individuals. Stem cells were purified, banked and used for a transcriptomic study. Two-colors experiment. The cohort was then paired with 11 age- and gender-matched control individuals. Stem cells were purified, banked and used for a transcriptomic study. Validation by reverse transcription design.

2014-11-22 | E-GEOD-63524 | biostudies-arrayexpress

Systemic effects of the long noncoding RNA COSMOC in autism spectrum disorders

Project description:Autism Spectrum Disorders are complex neurodevelopmental disorders often attributed to specific mutated genes that collectively affect less than 10% of autists. We recently identified MOCOS, a molybdenum cofactor sulfurase-coding gene that was downregulated in stem cells of most autists of a cohort, disturbing redox homeostasis and synaptogenesis. We now report that, upstream of MOCOS, a divergent transcription generates an antisense long noncoding RNA called COSMOC. Remarkably, COSMOC expression is very low in all patients of this cohort. Knockdown studies indicates that loss of COSMOC reduces MOCOS expression, destabilizes lipid metabolism and affects energy metabolism of stem cells. Moreover, COSMOC deficiency is associated with defective neuronal maturation through the splicing regulator PTBP2 and the postsynaptic scaffold protein PSD95 involved in synaptic transmission. This dysregulation of COSMOC/MOCOS bidirectional unit might explain the origin of the disease for most autists

2019-10-01 | GSE122434 | GEO

Factors regulating subcutaneous adipose tissue storage, fibrosis, and inflammation may underlie low systemic rates of fatty acid mobilization in insulin sensitive obese adults

Project description:Although the rate of fatty acid release from adipose tissue into the systemic circulation is very high in most obese adults, some obese adults maintain relatively low rates of fatty acid release, which helps protect them against the development of systemic insulin resistance. The primary aim of this study was to identify factors in adipose tissue that may underlie low vs. high rates of fatty acid mobilization in a relatively homogeneous cohort of obese adults. We obtained subcutaneous abdominal adipose tissue samples from 30 obese adults (BMI: 38±1 kg/m2, age: 30±2 yr) after an overnight fast. We performed microarray analysis on the adiose tissue samples.

2017-03-08 | GSE95777 | GEO

Cell size is a determinant of stem cell potential during aging (HSC treatments RNA-seq dataset)

Project description:Stem cells are remarkably small in size. Human hematopoietic stem cells (HSCs) measure a mere 7 μm in diameter. Whether small size is important for stem cell function is unknown. We find that murine HSCs enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferative potential. We further show that preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing the size of large HSCs by shortening G1 averts the loss of stem cell potential. Naturally large HSCs also exhibit decreased stem cell potential indicating that large size characterizes exhausted HSCs under physiological conditions. Finally, we show that our findings are relevant to aging. A fraction of murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function and propose that stem cell enlargement contributes to their functional decline during aging.

2021-09-19 | GSE154334 | GEO

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Gene expression-based, individualized outcome prediction for autism

Project description:Individualized outcome prediction classifiers were successfully constructed through expression profiling of 91 up-regulated and 67 down-regulated miRNAs in 5 autism spectrum disorder (ASD) cases and 5 controls. In the study presented here, a well-defined cohort of 5 autism spectrum disorder cases and 5 controls was used to acquire expression profiles of 91 up-regulated and 67 down-regulated miRNAs, leading to the first global miRNA expression profile of ASD in China.

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Transcriptome analysis of CHD8 ko mice

Project description:Autism Spectrum Disorders includes several behavioral phenotypes in addition to other comorbid conditions. One of the strongest comorbidities in Autism is gastrointestinal issues. Gastrointestinal issues are also prevalent in individuals with mutations in CHD8, which is one of the top autism-related genes. However, the relationship between autism related genes, such as CHD8, gastrointestinal function, and autism related behaviors are yet very unclear. In this study our goal is to explore the molecular mechanism and connection between CHD8 KO and gastrointestinal problems.

2021-08-29 | GSE182815 | GEO

Comparative analysis of glioblastoma initiating cells and patient-matched EPSC-derived neural stem cells as a discovery tool and drug matching strategy [Seq]

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2021-09-17 | GSE154367 | GEO

Comparative analysis of glioblastoma initiating cells and patient-matched EPSC-derived neural stem cells as a discovery tool and drug matching strategy [array]

Project description:Malignant gliomas are the most common intrinsic brain tumors in adults and are associated with a very poor prognosis, which has not improved in the last 20 years. We show here that glioblastoma initiating cells (GIC) and syngeneic neural stem cells derived from enhanced pluripotent stem cells (iNSC) are a suitable novel pre-clinical pipeline to discover new patient-specific disease mechanisms and to identify druggable targets for personalized therapy.

2021-09-17 | GSE155985 | GEO

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