SMRT compounds abrogate cellular phenotypes of Ataxia Telangiectasia in neural derivatives of patient specific hiPSCs
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: William Lowry
PROVIDER: E-GEOD-45030 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:gene expression profiling of WT fibroblasts, hiPSCs, and NPCs compared to the same cell types isolated from patients with Ataxia Telangiectasia gene expression profiling was carried out with Affymetrix Hg133 2.0 plus chips
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Project description:Detailed analysis comparing hiPSC lines that were newly generated and compared them to already established hiPSC lines We used microarrays to detail various hiPSC lines to confirm faithful reprogramming. hESCs, hiPSCs and human fibroblasts for RNA extraction and hybridization on Affymetrix arrays.
2010-08-06 | E-GEOD-22392 | biostudies-arrayexpress
Project description:In this study, we reprogrammed fibroblasts from two azoospermic Klinefelter syndrome (KS) patients, and two healthy male and one healthy female donor with an efficient integration-free method using episomal plasmids and laminin-521 (LN521). Whole genome transcriptomics analysis showed differentially expressed genes between KS and healthy male donors with enrichment in gene ontology (GO) terms associated with fertility, cardiovascular development, ossification and brain development, for both KS hiPSCs and fibroblasts, correlating with the KS clinical phenotype. Thorough XCI analysis combining transcriptomics data, RNA FISH and H3K27me3 staining, revealed skewed XCI in one KS fibroblast line and variability in XCI state of KS hiPSCs similar to female hiPSCs, showing either XaXi or XaXe status. Furthermore, we found up-regulated X-linked genes involved in nervous system development, synaptic transmission as well as metabolic processes supporting the potential use of KS derived hiPSC as an in vitro model for KS.
2019-10-05 | E-MTAB-7340 | biostudies-arrayexpress
Project description:In our study, PRDM14 and NFRkB were found to enhance the reprogramming of human fibroblasts to hiPSCs in the presence of OCT4, SOX2, KLF4, with/without c-MYC (OSK/OSKC). To examnie if the obtained hiPSC share similar expression signature with hESC, we conducted the microarray analysis on the hiPSCs, hESCs and fibroblasts. The result showed that all of the examined hiPSCs resembled hESCs, but differed from fibroblasts MRC5. 4 hiPSC lines, 2 hESC lines and 1 type of fibroblasts were analyzed in total. Each sample is done in duplicates.
2010-10-20 | E-GEOD-22792 | biostudies-arrayexpress
Project description:In our study, PRDM14 and NFRkB were found to enhance the reprogramming of human fibroblasts to hiPSCs in the presence of OCT4, SOX2, KLF4, with/without c-MYC (OSK/OSKC). To examnie if the obtained hiPSC share similar expression signature with hESC, we conducted the microarray analysis on the hiPSCs, hESCs and fibroblasts. The result showed that all of the examined hiPSCs resembled hESCs, but differed from fibroblasts MRC5.
2010-10-20 | GSE22792 | GEO
Project description:Ataxia Telangiectasia (AT) is a rare disorder characterized by neurodegeneration, combined immunodeficiency, predisposition to malignancies and high clinical variability. MicroRNAs (miRNAs) profiling may provide information on the pathophysiology of complex rare human diseases as they are involved in numerous biological functions including proliferation, differentiation, and DNA repair. To investigate the differential expression of miRNAs in AT patient samples with the aim of identifying miRNA signatures and correlate these patterns with disease pathogenesis. Twenty AT patients (mean age 17.7 + 9.6 years) were enrolled in the study. Clinical and genetic data were collected. We performed a small RNA-seq analysis in PBMCs and fibroblasts to compare miRNA expression profiles in AT patients and controls, and to identify specific expression signatures for AT. We found 42 differentially expressed (DE)-miRNAs in blood samples and 26 in fibroblasts samples. Three DE-miRNAs, miR-342-3p, miR-30a-5p, and miR-195-5p were validated in further AT samples and their dysregulation was confirmed.We identified for the first time, an AT-associated miRNA signature in blood cells and fibroblast samples obtained from a cohort of AT patients. Several pathways were predicted commonly deregulated, mainly involved in cancer. miRNAs may provide information on AT pathophysiology and tumorigenesis.
2024-10-01 | GSE266440 | GEO
Project description:Congenital Zika syndrome (CZS), caused by Zika virus (ZIKV) infection, has been associated to impairment of early brain development, particularly related to neural progenitor cells (NPCs) survival and growth. In this work we report in a high-throughput manner (RNA-Seq) the differences in the transcriptomes of hiPSCs(human induced pluripotent stem cells)-derived NPCs from 3 pairs of discordant twins for Congenital Zika syndrome (CZS). We found significant differences in the expression levels of genes relevant to the regulation of neural development between the NPCs from CZS-affected and non-affected twins, suggesting that epigenetic differences may contribute to the different susceptibilities of NPCs to ZIKV infection.
2018-02-27 | GSE102128 | GEO
Project description:The equivalency of human induced pluripotent stem cells (hiPSCs) with human embryonic stem cells (hESCs) remains controversial. Here, we devised a strategy to assess the contribution of clonal growth, reprogramming method and genetic background to transcriptional patterns in hESCs and hiPSCs. Surprisingly, transcriptional variation originating from two different genetic backgrounds was dominant over variation due to the reprogramming method or cell type of origin of pluripotent cell lines. Moreover, the few differences we detected between isogenic hESCs and hiPSCs neither predicted functional outcome, nor distinguished an independently derived, larger set of unmatched hESC/hiPSC lines. We conclude that hESCs and hiPSCs are transcriptionally and functionally highly similar and cannot be distinguished by a consistent gene expression signature. Our data further imply that genetic background variation is a major confounding factor for transcriptional comparisons of pluripotent cell lines, explaining some of the previously observed expression differences between unmatched hESCs and hiPSCs. Expression profiling of human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and fibroblasts, mostly in triplicates.
2015-10-26 | E-GEOD-73211 | biostudies-arrayexpress
Project description:The difficulty associated with generating induced pluripotent stem cells (iPSC) from patients with chromosomal instability syndromes suggests the cellular DNA damage response poses a barrier to reprogramming. Here we demonstrate that fibroblasts from patients with ataxia-telangiectasia (A-T) can be reprogrammed to bona-fide iPSC, albeit at a reduced efficiency. A-T iPSC display defective radiation-induced signaling, radiosensitivity and cell cycle checkpoint defects. Bioinformatic analysis of gene expression in the A-T iPSC identifies abnormalities in DNA damage signaling pathways as well as changes in mitochondrial and pentose phosphate pathways. A-T iPSC can be differentiated into functional neurons and thus represent a suitable model system to investigate A-T associated neurodegeneration. Collectively our data show that iPSC can be generated from a chromosomal instability syndrome and that these cells can be used to discover early developmental consequences of ATM deficiency, such as altered mitochondrial function, that may be relevant to A-T pathogenesis and amenable to therapeutic intervention. Three different cell types: fibroblasts, human embyronic stem cells, and induced pluripotent stem cells with heterozygote, homozygote A-T compared to normal samples.
2012-05-27 | E-GEOD-35347 | biostudies-arrayexpress
Project description:BackgroundAtaxia telangiectasia is one of the most common causes of autosomal recessive cerebellar ataxias. However, absence of telangiectasia, normal levels of alpha-fetoprotein and negative genetic test may direct to alternative diagnosis with similar phenotypes such as ataxia telangiectasia-like disorders (ATLD).CasesWe report two instructive cases of ATLD: the first case with ataxia telangiectasia-like disorder type 1 related to MRE11A gene, and the second case with ataxia telangiectasia-like disorder type 2 related to PCNA gene.Literature reviewATLD is an unusual group of autosomal recessive diseases that share some clinical features and pathophysiological mechanisms with ataxia telangiectasia (AT). ATLD may be associated with mutations in the MRE11A (ATLD type 1) and PCNA (ATLD type 2) genes. ATLD belongs to the group of chromosomal instability syndromes. The reason for the term ATLD is related to the similar pathophysiological mechanisms observed in AT, which is characterized by chromosomal instability and radiosensitivity.ConclusionsIn this review, the main clinical features, biomarkers, brain imaging and genetics of ATLD are discussed. Mutations in the MRE11A and PCNA genes should be included in the differential diagnosis for early onset cerebellar ataxia with absence of telangiectasia and normal levels of alpha-fetoprotein.
| S-EPMC7780949 | biostudies-literature