DNA microarrays of Turner Syndrome induced pluripotent stem cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE32527 | GEO | 2011/10/04
SECONDARY ACCESSION(S): PRJNA147829
REPOSITORIES: GEO
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Project description:We have generated iPSCs from monosomy X (Turner Syndrome), trisomy 8 (Warkany Syndrome 2), trisomy 13 (Patau Syndrome) and partial trisomy 11;22 (Emanuel Syndrome), using either skin fibroblasts from affected individuals or amniocytes from antenatal diagnostic tests. These cell lines stably maintain the karyotype of the donors and behave like embryonic stem cells (ESCs) in all tested assays. Turner Syndrome iPSCs were used for further studies including global gene expression analysis and tissue-specific directed differentiation. Multiple clones displayed lower levels of the pseudoautosomal genes ASMTL and PPP2R3B than the controls. Moreover, they could be transformed into neural-like, hepatocyte-like and heart-like cells but displayed insufficient up-regulation of the pseudoautosomal placental gene CSF2RA during embryoid body (EB) formation. These data support that abnormal organogenesis and early lethality in Turner Syndrome are not caused by a tissue-specific differentiation blockade but rather involves other abnormalities including impaired placentation. Global gene expression profiling with DNA microarrays showed that 3 TS iPSC clones corresponding to the same patient showed a global gene expression pattern similar to ESCs and euploid iPSCs, and very different from donor cells .We detected transcriptomic changes between TS iPSCs and the other ESCs/iPSCs but these variations did not follow a pattern and in fact all pluripotent cell lines clustered together. For DNA microarray analysis, all cells were treated with Trizol, followed by RNA extraction and hybridization.
2011-10-03 | E-GEOD-32527 | biostudies-arrayexpress
Project description:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChip® Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a “Turner syndrome core transcriptome”), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study.
2014-06-13 | GSE58435 | GEO
Project description:Background: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome. Methods: Global gene expression analysis was performed utilizing cell-free RNA from five midtrimester fetuses with Turner syndrome matched with five euploid female fetuses. Total RNA was extracted, amplified, hybridized onto GeneChipM-BM-. Human Genome U133 Plus 2.0 arrays. Network and pathway analysis of differentially expressed genes were completed. Chromosomal distribution of gene expression differences, differential expression by pathway and organ system (a M-bM-^@M-^\Turner syndrome core transcriptomeM-bM-^@M-^]), and candidate genes that could play a pathological role were identified. Results: There were 470 differentially expressed genes identified in the Turner syndrome transcriptome. The differentially expressed genes were distributed randomly across different chromosomes. Among genes on the X chromosome, XIST was down-regulated, and SHOX not differentially expressed. The most highly represented organ systems were hematologic/immune and neurologic. Increased representation of differentially expressed genes in the hematologic/immune system distinguishes the Turner syndrome transcriptome from the euploid, trisomy 18 and trisomy 21 transcriptomes previously studied in our laboratory. Manual curation of the differentially expressed gene list identified genes including NFATC3, IGFBP5, and LDLR that warrant further study. 2nd trimester amniotic fluid mRNA expression was compared between 5 Turners and 5 euploid fetuses.
2014-06-13 | E-GEOD-58435 | biostudies-arrayexpress
Project description:The interaction between germ cells and somatic cells in the ovaries plays a crucial role in establishing the follicle reserve in mammals. Turner syndrome (TS) predominantly occurs in females who have either a partial or complete loss of one of their X chromosomes. Our understanding of the role granulosa cells (GCs) play in TS disease progression and pathogenesis remains limited. Here, we elevated GC differentiation efficiency up to the level of 80% differentiated cells from iPSCs. In our attempt to replicate the differentiation process of embryonic granulosa cells, we observed that specific genes—GATA4, FOXL2, AMHR2, CYP19A1, and FSH—were downregulated in Turner syndrome-derived granulosa cells (TS-GCs). Additionally, dysregulation of the cell cycle was observed in TS-GCs. To reveal the endogenous defects in the TS-GCs, we conducted a comparison of the global transcriptome patterns between differentiated granulosa cells derived from iPSCs in both healthy and Turner syndrome groups. The apelin/APJ pathway displayed a differential between the healthy and TS groups. Supplementation of apelin ligands and activation of apelin/APJ downstream signals via Akt/PKB restored the cell cycle progression and marker gene expression. We hypothesize that during early embryonic development failures in apelin/APJ signaling in GCs in Turner syndrome patients leads to abnormalities in ovarian development and consequently to early loss of oocytes and infertility.
2024-11-20 | GSE271780 | GEO
Project description:Background:Human aneuploidy is the leading cause of early pregnancy loss, mental retardation, and multiple congenital anomalies. Due to the high mortality associated with aneuploidy, the pathophysiological mechanisms of aneuploidy syndrome remain largely unknown. Previous studies focused mostly on whether dosage compensation occurs, and the next generation transcriptomics sequencing technology RNA-seq is expected to eventually uncover the mechanisms of gene expression regulation and the related pathological phenotypes in human aneuploidy. Results:Using next generation transcriptomics sequencing technology RNA-seq, we profiled the transcriptomes of four human aneuploid induced pluripotent stem cell (iPSC) lines generated from monosomy X (Turner syndrome), trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome), and partial trisomy 11:22 (Emanuel syndrome) as well as two umbilical cord matrix iPSC lines as euploid controls to examine how phenotypic abnormalities develop with aberrant karyotype. A total of 466 M (50-bp) reads were obtained from the six iPSC lines, and over 13,000 mRNAs were identified by gene annotation. Global analysis of gene expression profiles and functional analysis of differentially expressed (DE) genes were implemented. Over 5000 DE genes are determined between aneuploidy and euploid iPSCs respectively while 9 KEGG pathways are overlapped enriched in four aneuploidy samples. Conclusions:Our results demonstrate that the extra or missing chromosome has extensive effects on the whole transcriptome. Functional analysis of differentially expressed genes reveals that the genes most affected in aneuploid individuals are related to central nervous system development and tumorigenesis. Four aneuploid iPSC (trisomy 8, trisomy 13, partial trisomy 11:22, monosomy X) and two euploid iPSC mRNA profiles were generated by deep sequencing, using SOLiD v3 platform. Gene expression values were compared.
2013-09-24 | E-GEOD-49247 | biostudies-arrayexpress
Project description:Background: Among full autosomal trisomies, only trisomies of chromosome 21 (Down syndrome, DS), 18 (Edward syndrome, ES) and 13 (Patau syndrome, PS) are compatible with postnatal survival. But the mechanisms, how a supernumerary chromosome disrupts the normal development and causes specific phenotypes, are still not fully explained. As an alternative to gene dosage effects due to the trisomic chromosome, a genome-wide transcriptional dysregulation has been postulated. The aim of this study was to define the transcriptional changes in trisomy 13, 18, and 21 during early fetal development in order to define whether (1) overexpression of genes of the trisomic chromosome contributes solely to the phenotype, if (2) all genes of the trisomic chromosome are upregulated similarly and whether the ratio of gene expression is in agreement with the gene dosis, (3) whether the different trisomies behave similarly in the characteristics of transcriptional dysregulation, and (4) whether transcriptional pattern can be potentially used in prenatal diagnosis. Methods: Using oligonucleotide microarrays (Affymetrix, U133 Plus 2.0), we analyzed whole genome expression profiles representing 54.000 probe sets in cultured amniocytes (AC) and chorion villus cells (CV) from pregnancies with a normal karyotype and with trisomies of human chromosomes 21, 18 and 13. Findings: We observed a low to moderate up-regulation for a subset of genes of the trisomic chromosomes. Transcriptional level of approximately 12-13 % of the supernumerary chromosome appeared similar to the respective chromosome pair in normal karyotypes. Expression values as well as the expression patterns of genes from the trisomic chromosome can distinguish the respective trisomic samples from euploid controls. A subset of chromosome 21-genes including the DSCR1-gene involved in fetal heart development was consistently up-regulated in different tissues (AC, CV) of trisomy 21 fetuses whereas only minor changes were found for genes of all other chromosomes. In contrast, in trisomy 13 and trisomy 18 vigorous downstream transcriptional changes were found. Interpretation: Global transcriptome analysis for autosomal trisomies 13, 18, and 21 supported a combination of the two major hypotheses. As several transcriptional pathways are altered, complex regulatory mechanisms are involved in the pathogenesis of autosomal trisomies. A genome-wide transcriptional dysregulation was predominantly observed in trisomies 13 and 18, whereas a more to chromosome 21 restricted expression alteration was found in trisomy 21. Keywords: Trisomy, Down syndrome, Patau syndrome, Edward syndrome, microarray, gene expression, amniocytes, chorion villus cells, gene dosage effect, DSCR1
2006-12-01 | GSE6283 | GEO
Project description:Background:Human aneuploidy is the leading cause of early pregnancy loss, mental retardation, and multiple congenital anomalies. Due to the high mortality associated with aneuploidy, the pathophysiological mechanisms of aneuploidy syndrome remain largely unknown. Previous studies focused mostly on whether dosage compensation occurs, and the next generation transcriptomics sequencing technology RNA-seq is expected to eventually uncover the mechanisms of gene expression regulation and the related pathological phenotypes in human aneuploidy. Results:Using next generation transcriptomics sequencing technology RNA-seq, we profiled the transcriptomes of four human aneuploid induced pluripotent stem cell (iPSC) lines generated from monosomy X (Turner syndrome), trisomy 8 (Warkany syndrome 2), trisomy 13 (Patau syndrome), and partial trisomy 11:22 (Emanuel syndrome) as well as two umbilical cord matrix iPSC lines as euploid controls to examine how phenotypic abnormalities develop with aberrant karyotype. A total of 466 M (50-bp) reads were obtained from the six iPSC lines, and over 13,000 mRNAs were identified by gene annotation. Global analysis of gene expression profiles and functional analysis of differentially expressed (DE) genes were implemented. Over 5000 DE genes are determined between aneuploidy and euploid iPSCs respectively while 9 KEGG pathways are overlapped enriched in four aneuploidy samples. Conclusions:Our results demonstrate that the extra or missing chromosome has extensive effects on the whole transcriptome. Functional analysis of differentially expressed genes reveals that the genes most affected in aneuploid individuals are related to central nervous system development and tumorigenesis.
2013-09-24 | GSE49247 | GEO
Project description:Heart deformity is the leading cause of mortality in Turner syndrome (TS) patients. To investigate the dysregulated ceRNA network in cardiomyocytes (CMs) of TS patients, we employed a ceRNA microarray to profile the mRNA-lncRNA-circRNA network in induced pluripotent stem cells (iPSCs) and their derived CMs from healthy donors (WT) and TS patients.
2023-08-06 | GSE239758 | 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. Experiment Overall Design: We used DNA microarray to measure the differences in gene expression variance (representing variation) between four human trisomy 21 amniocytes and six human euploid amniocytes.
2008-04-03 | E-GEOD-10758 | biostudies-arrayexpress
Project description:DNA Methylation Analysis of Turner Syndrome BAV
| PRJNA814295 | ENA