Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA260081 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Ataxia-telangiectasia cerebellar cortex expression
2025-01-24 | E-GEOD-61019 | ExpressionAtlas
Project description:Cerebellar differentiation in Ataxia-Telangiectasia
| PRJNA305532 | ENA
Project description:Cerebellar cortex expression in ataxia-telangiectasia patients and normal controls. The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency. Human frozen tissue was obtained from the NICHD Brain and Tissue Bank of Developmental Disorders at the University of Maryland, Baltimore, MD. RNA was prepared and run on an Illumina Human HT-12 v4 microarray. 3 ataxia-telangiectasia (A-T) cases and 4 normal controls.
2015-10-30 | E-GEOD-61019 | biostudies-arrayexpress
Project description:Cerebellar cortex expression in ataxia-telangiectasia patients and normal controls. The neurodegenerative disease known as ataxia-telangiectasia (A-T) is caused by the absence of the ATM (A-T mutated) protein. A long-standing mystery surrounding A-T is why cerebellar Purkinje cells (PCs) appear uniquely vulnerable to ATM-deficiency. Here, we present that 5-hydroxymethylcytosine (5hmC), a newly recognized epigenetic marker found at high levels in neurons, is substantially reduced in human A-T and Atm-/- mouse cerebellar PCs. TET1, an enzyme that converts 5mC to 5hmC, responds to DNA damage. Manipulation of TET1 activity directly affects neuronal cell cycle reentry and cell death after the induction of DNA damage. Quantitative, genome-wide analysis of 5hmC of samples from human cerebellum showed that in ATM-deficiency there is a remarkable genome-wide reduction of 5hmC enrichment at both proximal and distal regulatory elements. These results reveal a role of TET1-mediated 5hmC in DNA damage response, and provide insights into the basis of a PC-specific DNA demethylation alteration in ATM-deficiency.
2015-10-30 | GSE61019 | GEO
Project description:Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks
2025-01-24 | E-GEOD-75852 | ExpressionAtlas
Project description:Background & Aims: Loss of ataxia-telangiectasia mutated, occurring in patients with multiple primary malignancies, including pancreatic cancer, is associated with poor prognosis. This study investigated the detailed molecular mechanism through which ataxia-telangiectasia mutated expression affects the prognosis of pancreatic-cancer patients Methods: Ataxia-telangiectasia mutated and phosphorylated ataxia-telangiectasia mutated levels in pancreatic-cancer patients who underwent surgical resection were analyzed using immunohistochemistry staining. RNA sequencing was performed on ataxia-telangiectasia mutated-knockdown pancreatic-cancer cells to elucidate the mechanism underlying the involvement of ataxia-telangiectasia mutated in pancreatic cancer. Results: Immunohistochemical analysis showed that 15.3% and 27.8% of clinical samples had low levels of ataxia-telangiectasia mutated and phosphorylated ataxia-telangiectasia mutated, respectively. Low phosphorylated ataxia-telangiectasia mutated expression substantially reduced overall and disease-free survival in pancreatic-cancer patients. Loss of ataxia-telangiectasia mutated promoted MET and NTN1 over-expression via hypoxia-inducible factor-1α, thereby enhancing pancreatic-cancer cell proliferation and migration. Conclusions: These results demonstrate that the loss of ataxia-telangiectasia mutated activates downstream proto-oncogenes, inhibits apoptosis, and promotes tumor growth; moreover, loss of phosphorylated ataxia-telangiectasia mutated leads to poor prognosis in pancreatic-cancer patients. Thus, ataxia-telangiectasia mutated may serve as a potential molecular marker to monitor patient prognosis and as a potential target for pancreatic cancer therapy
2023-02-13 | GSE224882 | GEO
Project description:ATM (ataxia telangiectasia mutated) kinase is crucial to a wide range of human developmental disorders and adult/pediatric malignancies. Its mutations are causally tied to ataxia telangiectasia, a multi-systemic congenital disorder mainly affecting brain and blood systems. We generated 4 separate ATM-knockout human pluripotent stem cell lines and differentiated them to form 3-dimensional brain cortical brain organoids. Brain cortical organoids are an excellent model of human developing cortex. Using these analyses, we identified ATM-dependent phosphorylation predominantly influences factors in neurogenesis, neuronal differentiation, cell morphogenesis, and microtubule cytoskeleton as well as kinases involved in ATM, BNDF, and WNT signaling, G2/M checkpoint, and p53 regulation. These findings have broad implications about diseases associated with ATM, including ataxia telangiectasia.
2024-07-25 | PXD041699 | Pride
Project description:An induced pluripotent stem cell model for ataxia telangiectasia
| PRJNA152721 | ENA
Project description:Australian working Kelpie dogs are known to be affected with an autosomal recessive form of inherited cerebellar ataxia (cerebellar abiotrophy, CA) that is characterised by a degeneration of Purkinje and granule cells in the cerebellar cortex. The clinical signs of CA include cerebellar ataxia, head tremor, motor in-coordination, wide based stance and high stepping gait, with varied clinical onset age. The clinical and pathological features are similar to cerebellar ataxias in humans. The genome-wide association study on a group of working Kelpies affected with the later onset form of CA identified a region on chromosome 9 to be strongly associated with the disease phenotype. Homozygosity analysis and whole genome sequencing identified a missense single nucleotide polymorphism, that segregated with the CA phenotype.
2022-12-31 | GSE102154 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO