RNA sequencing of Timothy syndrome human cortical and subpalial organoids
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE175898 | GEO | 2021/10/20
REPOSITORIES: GEO
Similar Datasets
Project description:We derived iPSC from individuals carrying a 22q11.2 deletion and controls and differentiated them into 3D cortical organoids.
2020-07-08 | GSE142041 | GEO
Project description:RNA sequencing of Timothy syndrome human cortical and subpalial organoids
| PRJNA734273 | ENA
Project description:Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Cav1.2 that is associated with developmental delay and autism. We generated cortical neuronal precursor cells and neurons from induced pluripotent stem cells derived from individuals with Timothy syndrome. Cells from these individuals have defects in calcium (Ca2+) signaling and activity-dependent gene expression and show abnormalities in differentiation. Neurons from individuals with Timothy syndrome show increased expression of markers of the upper cortical layer and decreased expression of callosal projection markers. In addition, the mutation that causes Timothy syndrome leads to an increase in the production of neurons that synthesize norepinephrine and dopamine. This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase and atypical L-type–channel blocker. These findings provide strong evidence that Cav1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome. Total RNA was isolated from control and TS cells: fibroblasts, iPSCs, neurospheres (at day 7 in suspension), neurons at rest (day 45 of differentiation) and neurons kept in 67mM KCl for 9h. For sample titles, D1,D2 and D3 represent independent differentiation experiments. The number after - represents the iPSC cell line number. GSE25542_non-normalized.txt.gz contains data for 5 outliers.
2011-11-07 | E-GEOD-25542 | biostudies-arrayexpress
Project description:Here we used human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Cortical organoids were differentiated as previously described (Paşca et al., 2015, doi: 10.1038/nmeth.3415.).Chronic GSK3 inhibition was performed by adding CHIR99021 (Merck SML1046) to the medium at day 0 (1 microM) and kept throughout the differentiation process until reaching the respective collection timepoints (day 18, day 50, day 100).
2020-06-04 | E-MTAB-8325 | biostudies-arrayexpress
Project description:Monogenic neurodevelopmental disorders provide key insights into the pathogenesis of disease and help us understand how specific genes control the development of the human brain. Timothy syndrome is caused by a missense mutation in the L-type calcium channel Cav1.2 that is associated with developmental delay and autism. We generated cortical neuronal precursor cells and neurons from induced pluripotent stem cells derived from individuals with Timothy syndrome. Cells from these individuals have defects in calcium (Ca2+) signaling and activity-dependent gene expression and show abnormalities in differentiation. Neurons from individuals with Timothy syndrome show increased expression of markers of the upper cortical layer and decreased expression of callosal projection markers. In addition, the mutation that causes Timothy syndrome leads to an increase in the production of neurons that synthesize norepinephrine and dopamine. This phenotype can be reversed by treatment with roscovitine, a cyclin-dependent kinase and atypical L-type–channel blocker. These findings provide strong evidence that Cav1.2 regulates the differentiation of cortical neurons in humans and offer new insights into the causes of autism in individuals with Timothy syndrome.
2011-11-07 | GSE25542 | GEO
Project description:22q11.2 deletion syndrome human cortical organoids
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Project description:Retinitis pigmentosa (RP) is an irreversible and inherited retinopathy. RPGR mutations are the most common causes of this disease. It remains challenging to decipher the mechanism of RPGR mutation because of the lack of appropriate study models. The substitution of patient-specific diseased retina without ethical restrictions is desired and iPSC-derived 3D retina is the best choice. In our experiment, we generated iPSCs from one RP patient with 2-bp frameshift mutation in the exon14 of RPGR gene, which were differentiated into retinal organoids. Also we generated iPSCs from a normal control and differentiated those control-iPSCs into healthy retinal organoids. Samples of patient- and control-retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates for patient) were collected for RNA-seq. Corrected-iPSC were derived from CRISPR/Cas9-mediated gene correction. Then we collected the corrected-iPSC derived retinal organoids at W0, W7, W13 (two replicates), W18 (two replicates) and W22 (two replicates) for RNA-seq. Through the RNA-seq data, we demonstrate that patient-specific iPSC-dervied 3D retinae can recapitulate disease progress of Retinitis Pigmentosa through presenting defects in photoreceptors' gene profile. CRISPR/Cas9-mediated gene correction can rescue photoreceptor gene profile. Those transcriptome are consistent with the phenotype and function.
2020-02-01 | E-MTAB-6490 | biostudies-arrayexpress
Project description:This study aims to gather information on iPSC-derived cortical brain organoids differentiated in six different time points. Bulk RNA sequencing (RNA-seq) was performed at days 3, 4, 5, 20, 25, and 32 post-initiation of differentiation. The resulting dataset provides a foundational control reference for assessing the roles of various transcription factors previously manipulated in cortical organoid models.
2025-09-01 | GSE303979 | GEO
Project description:Here we used human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Cortical organoids were differentiated as previously described (Paşca et al., 2015, doi: 10.1038/nmeth.3415.). Chronic GSK3 inhibition was performed by adding CHIR99021 (Merck SML1046) to the medium at day 0 (1 microM) and kept throughout the differentiation process until reaching the respective collection timepoints (day 50, day 100).
2020-06-09 | E-MTAB-8337 | biostudies-arrayexpress
Project description:Smith-Magenis syndrome (SMS) is a genomic disorder caused by the deletion of a chromosomal region at 17p11.2. Individuals with SMS are frequently diagnosed with autism and have profound cortical deficits, including reduced cortex volume, mild ventriculomegaly, and epilepsy. Here, we developed human induced pluripotent stem cell (hiPSC)-derived neuronal models to understand how del(17)p11.2 affects cortical development. Hi-C identified local fusion and global reorganization of topological domains, as well as genome-wide miswiring of chromatin 3-dimensional (3D) interactions in SMS hiPSC and 3D cortical organoids. Single-nucleus RNA-seq of SMS cortical organoids identified neuropsychiatric disease-enriched transcriptional signatures and dysregulation of genes involved in catabolic and biosynthetic pathways, cell cycle processes, and neuronal signalling. SMS cortical organoids had reduced growth, enlarged ventricles, and impaired cell cycle progression. In a complementary hiPSC-derived 2D cortical neuronal model, we found SMS cortical neurons had accelerated dendritic growth, followed by neuronal hyperexcitability that was associated with a reduced potassium conductance. Our study demonstrates that del(17)p11.2 disrupts multiple steps of human cortical development, from chromatin wiring, transcriptional regulation, cell cycle progression, and morphological maturation to neurophysiological properties, and hiPSC-derived models recapitulate key neuroanatomical and neurophysiological features of SMS.
2025-08-28 | GSE295166 | GEO