Partial monosomy 21 mirrors gene expression of trisomy 21 in a patient-derived neuroepithelial stem cells model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA785642 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17101515_1.fastq.gz | Fastqsanger.gz | |||
| SRR17101515_2.fastq.gz | Fastqsanger.gz | |||
| SRR17101516_1.fastq.gz | Fastqsanger.gz | |||
| SRR17101516_2.fastq.gz | Fastqsanger.gz | |||
| SRR17101517_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:Induced pluripotent stem cells (iPSCs) from patients are an attractive disease model to study tissues with poor accessibility such as the brain. Using this approach, we and others have shown that trisomy 21 results in genome-wide transcriptional dysregulations. The effects of loss of genes on chromosome 21 is much less characterized. Here, we use patient-derived neural cells from an individual with neurodevelopmental delay and a ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, containing 60 protein-coding genes. To investigate the molecular perturbations of the partial monosomy on neural cells, we established patient-derived iPSCs from fibroblasts retaining the ring chromosome 21, and we then induced iPSCs into neuroepithelial stem cells (NESCs). RNA-Seq analysis of NESCs with the ring chromosome revealed downregulation of 18 genes within the deleted region together with global transcriptomic dysregulations when compared to euploid NESCs. Since the deletions on chromosome 21 represent a genetic “contrary” to trisomy of the corresponding region, we further compared the dysregulated transcriptomic profile in with that of two NESC lines with trisomy 21. The analysis revealed opposed expression changes for 23 genes on chromosome 21 as well as 149 non-chromosome 21 genes. Taken together, our results bring insights into the effects on the global and chromosome 21 specific gene expression from a partial monosomy of chromosome 21qter during early neuronal differentiation.
2022-01-09 | GSE190053 | GEO
Project description:Induced pluripotent stem cells (iPSCs) from patients are an attractive disease model to study tissues with poor accessibility such as the brain. Using this approach, we and others have shown that trisomy 21 results in genome-wide transcriptional dysregulations. The effects of loss of genes on chromosome 21 is much less characterized. Here, we use patient-derived neural cells from an individual with neurodevelopmental delay and a ring chromosome 21 with two deletions spanning 3.8 Mb at the terminal end of 21q22.3, containing 60 protein-coding genes. To investigate the molecular perturbations of the partial monosomy on neural cells, we established patient-derived iPSCs from fibroblasts retaining the ring chromosome 21, and we then induced iPSCs into neuroepithelial stem cells. RNA-Seq analysis of NESCs with the ring chromosome revealed downregulation of 18 genes within the deleted region together with global transcriptomic dysregulations when compared to euploid NESCs. Since the deletions on chromosome 21 represent a genetic "contrary" to trisomy of the corresponding region, we further compared the dysregulated transcriptomic profile in with that of two NESC lines with trisomy 21. The analysis revealed opposed expression changes for 23 genes on chromosome 21 as well as 149 non-chromosome 21 genes. Taken together, our results bring insights into the effects on the global and chromosome 21 specific gene expression from a partial monosomy of chromosome 21qter during early neuronal differentiation.
| S-EPMC8854775 | biostudies-literature
Project description:Aneuploidies of human chromosome 21 (Down syndrome (DS) and monosomy 21 (M21)) lead to variable physiological abnormalities with constant mental retardation, locomotor deficits and altered muscle tone. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models carrying either tandem duplication (Ts2Yah) or a deletion (Ms3Yah) of the Stch-App interval homologous and syntenic with 21q11.2-q21.3 in humans. Here we report the complex mirror phenotypes of the trisomy and monosomy involving locomotion, muscle strength, mass and energetic balance that vary while ageing. Expression profiling of skeletal muscles revealed global changes in the expression of genes implicated in energetic metabolism, mitochondrial activity and biogenesis with down-regulation in Ts2Yah and up-regulation in Ms3Yah mice. The shift in skeletal muscle metabolism correlated with a change in mitochondrial proliferation without an alteration of the respiratory function. However ROS production from mitochondrial complex I decreased in Ms3Yah mice while membrane permeability of Ts2Yah mitochondria slightly increased. Our results clearly demonstrate the central versus peripheral impact of the variation of copy number of the Stch-App region on the locomotor activity, muscle biology and mitochondrial biogenesis in models of these aneuploidies.
2015-12-31 | GSE58463 | GEO
Project description:Aneuploidies of human chromosome 21 (Down syndrome (DS) and monosomy 21 (M21)) lead to variable physiological abnormalities with constant mental retardation, locomotor deficits and altered muscle tone. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models carrying either tandem duplication (Ts2Yah) or a deletion (Ms3Yah) of the Stch-App interval homologous and syntenic with 21q11.2-q21.3 in humans. Here we report the complex mirror phenotypes of the trisomy and monosomy involving locomotion, muscle strength, mass and energetic balance that vary while ageing. Expression profiling of skeletal muscles revealed global changes in the expression of genes implicated in energetic metabolism, mitochondrial activity and biogenesis with down-regulation in Ts2Yah and up-regulation in Ms3Yah mice. The shift in skeletal muscle metabolism correlated with a change in mitochondrial proliferation without an alteration of the respiratory function. However ROS production from mitochondrial complex I decreased in Ms3Yah mice while membrane permeability of Ts2Yah mitochondria slightly increased. Our results clearly demonstrate the central versus peripheral impact of the variation of copy number of the Stch-App region on the locomotor activity, muscle biology and mitochondrial biogenesis in models of these aneuploidies. Total RNA isolated from gastrocnemius muscles of mice that are trisomic (Ts2Yah) and monosomic (Ms3Yah) for the Stch-App region on Mmu16 and diploid control mice
2015-12-31 | E-GEOD-58463 | biostudies-arrayexpress
Project description:Gene expression was measured in trisomy 21 and trisomy 13 human fetal samples. For TS21, regions assayed were cerebrum, cerebellum, heart, and cerebrum-derived astrocyte cell lines. Keywords = trisomy 21 Keywords = Down syndrome Keywords = aneuploidy Keywords = brain Keywords = heart Keywords = trisomy 13 Keywords: other
2005-05-10 | GSE1397 | GEO
Project description:RNA-seq of lymphoblastoid cells from a family of individuals (one of which has Trisomy 21) was used to determine the molecular origin of dosage compensation in Trisomy 21.
2023-04-29 | GSE230995 | GEO
Project description:GRO-seq of lymphoblastoid cells from a family of individuals (one of which has Trisomy 21) was used to determine the molecular origin of dosage compensation in Trisomy 21.
2023-04-29 | GSE230994 | GEO
Project description:Down syndrome, caused by trisomy 21, is a complex developmental disorder associated with intellectual disability and reduced growth of multiple organs. Structural pathologies are present at birth, reflecting embryonic origins. A fundamental unanswered question is how an extra copy of human chromosome 21 contributes to organ-specific pathologies that characterize individuals with Down syndrome. Relevant to the hallmark intellectual disability in Down syndrome, how does trisomy 21 affect neural development? We tested the hypothesis that trisomy 21 exerts effects on human neural development as early as neural induction. Bulk RNA sequencing was performed on isogenic trisomy 21 and euploid human induced pluripotent stem cells (iPSCs) at successive stages of neural induction: embryoid bodies at Day 6, early neuroectoderm at Day 10, and differentiated neuroectoderm at Day 17. Gene expression analysis revealed over 1,300 differentially expressed genes in trisomy 21 cells along the differentiation pathway compared to euploid controls. Less than 5% of the gene expression changes included upregulated chromosome 21 encoded genes at every timepoint. Genes involved in specific growth factor signaling pathways (Wnt and Notch), metabolism (including interferon response and oxidative stress), and extracellular matrix were altered in trisomy 21 cells. Further analysis revealed heterochronic expression of genes. This comprehensive analysis reveals that trisomy 21 impacts discrete developmental pathways at the earliest stages of neural development. Further, the results suggest that metabolic dysfunction arises early in embryogenesis in trisomy 21 and may thus affect development and function more broadly.
2024-01-31 | GSE247990 | GEO
Project description:Congenital development disorders with variable severity occur in trisomy 21. However, how these phenotypic abnormalities develop with variations remains elusive. We hypothesize that the difference in euploidy gene expression variation among trisomy 21 tissues are perturbed by the presence of an extra copy of chromosome 21 and this may contribute to the phenotypic variations in Down syndrome. Keywords: Disease state analysis
2008-03-18 | GSE10758 | GEO
Project description:Molecular consequences of trisomy in lymphoblastoid cell lines from patients with Down syndrome. This project analyses differentially expressed genes between humans with trisomy 21 and humans without trisomy 21.
2012-08-15 | GSE34458 | GEO