Expression data from early postnatal brain in autism model marmoset
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ABSTRACT:
PROVIDER: PRJNA657011 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Autism spectrum disorder (ASD) affects gene expression in early postnatal development. We used valproic acid (VPA)-induced ASD model marmosets. Gene expression in VPA-exposed and unexposed (UE) marmosets were analyzed at 0, 3 and 6 months (M). We revealed three groups of differentially expressed genes based on the temporal patterns of modulation.
2021-04-01 | GSE156186 | GEO
Project description:Maternal autoantibody related autism (MARA), in which mothers produce specific patterns of autoantibodies during pregnancy, resulting in an autism diagnosis in their offspring, has been observed clinically. Multiple patterns of MARA autoantibodies have been identified clinically, and differences in the severity of the autism phenotype based on the autoantibody pattern have been described. In this study we utilized our preclinical rat model to further elucidate the differential effects of MARA autoantibody exposure based on the known clinical patterns, including the originally identified pattern of lactate dehydrogenase A and B (LDHA/B) + collapsin response mediator protein 1 (CRMP1) + stress-induced phosphoprotein 1 (STIP1) as well as the newly described patterns of CRMP1+CRMP2, CRMP1 + guanine deaminase (GDA), and STIP1+ neuron-specific enolase (NSE). We found that, at postnatal day 2, the levels of brain-specific and serum cytokines/chemokines were altered based on the pattern of MARA autoantibody exposure. Further, we observed changes in the brain transcriptomic profiles that suggest cellular proliferation and differentiation changes due to MARA exposure.
2025-07-02 | GSE275431 | GEO
Project description:Reciprocal deletion and duplication of 16p11.2 is the most common copy number variation (CNV) associated with Autism Spectrum Disorder (ASD) and other developmental disorders, and has significant effect on brain size. We used cortical organoids derived from ASD cases to investigate neurodevelopmental pathways dysregulated by dosage changes of 16p11.2 CNV. We show that organoids recapitulate patients’ macrocephaly and microcephaly phenotypes. Deletions and duplications have “mirror” effects on cell proliferation, maturation and synapse number, consistent with “mirror” effects on brain development in humans. Neuronal migration was decreased in both, deletion and duplication organoids. Transcriptomic and proteomic profiling revealed synaptic defects and neuronal migration as key drivers of 16p11.2 functional effect. We implicate upregulation of small GTPase RhoA involved in regulation of cytoskeletal dynamics, neuron migration and neurite outgrowth as one of the pathways impacted by the 16p11.2 CNV in ASD. Treatment with the RhoA inhibitor Rhosin rescued neuron migration, but not synaptic defects. This study identifies pathways dysregulated by the 16p11.2 CNV during early neocortical development using cortical organoid models. Grant ID: Simons Foundation, #345469 Grant Title: Translational dysregulation of the RhoA pathway in autism Affiliation: University of California San Diego Name: Lilia M. Iakoucheva; Alysson R. Muotri
2021-07-31 | GSE142174 | GEO
Project description:The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
2020-06-25 | GSE150537 | GEO
Project description:The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
2020-06-25 | GSE150536 | GEO
Project description:Autism spectrum disorder (ASD) is a common, highly heritable neuro-developmental condition characterized by marked genetic heterogeneity. Thus, a fundamental question is whether autism represents an etiologically heterogeneous disorder in which the myriad genetic or environmental risk factors perturb common underlying molecular pathways in the brain. Here, we demonstrate consistent differences in transcriptome organization between autistic and normal brain by gene co-expression network analysis. Remarkably, regional patterns of gene expression that typically distinguish frontal and temporal cortex are significantly attenuated in the ASD brain, suggesting abnormalities in cortical patterning. We further identify discrete modules of co-expressed genes associated with autism: a neuronal module enriched for known autism susceptibility genes, including the neuronal specific splicing factor A2BP1/FOX1, and a module enriched for immune genes and glial markers. Using high-throughput RNA-sequencing we demonstrate dysregulated splicing of A2BP1-dependent alternative exons in ASD brain. Moreover, using a published autism GWAS dataset, we show that the neuronal module is enriched for genetically associated variants, providing independent support for the causal involvement of these genes in autism. In contrast, the immune-glial module showed no enrichment for autism GWAS signals, indicating a non-genetic etiology for this process. Collectively, our results provide strong evidence for convergent molecular abnormalities in ASD, and implicate transcriptional and splicing dysregulation as underlying mechanisms of neuronal dysfunction in this disorder. Total RNA was extracted from approximately 100mg of postmortem brain tissue representing Cerebellum (C), Frontal cortex (F), and Temporal cortex (T), from autistic and control individuals.
2011-05-01 | E-GEOD-28521 | biostudies-arrayexpress
Project description:The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
2020-06-25 | GSE150534 | GEO
Project description:The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
2020-06-25 | GSE150532 | GEO
Project description:The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
2020-06-25 | GSE150531 | GEO
Project description:The maturation of the mammalian brain occurs after birth, and this stage of neuronal development is frequently impaired in neurological disorders, such as autism and schizophrenia. However, the mechanisms that regulate postnatal brain maturation are poorly defined. By purifying neuronal subpopulations across brain development in mice, we identify a postnatal switch in the transcriptional regulatory circuits that operates in the maturing mammalian brain. We show that this developmental transition includes the formation of hundreds of cell-type-specific neuronal enhancers in the postnatal period that might in part be modulated by neuronal activity. Once selected, these enhancers are active throughout adulthood, suggesting that their formation in early life shapes neuronal identity and regulates mature brain function.
2020-06-25 | GSE150535 | GEO