Expression data from human trisomy 21 and euploid fibroblasts, iPSCs, and neural progenitor cells
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ABSTRACT:
PROVIDER: PRJNA1143483 | ENA |
REPOSITORIES: ENA
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Project description:Trisomy of human chromosome 21 (T21) gives rise to Down syndrome, the most frequent life-born autosomal aneuploidy. To enable in vitro analyses of the cellular and moelcular mechanisms leading to the neurological alterations associated with T21, we created and characterized a panel of genomically diverse T21 and euploid induced pluripotent stem cells (iPSCs) from fibroblasts obtained from the Coriell Institute for Biomedical Research, and we then differentiated these iPSCs into neural progenitor cells (NPCs). Microarray transcriptomic analyses were performed on this panel of fibroblasts, iPSCs, and NPCs, identifying genes and pathways that were altered in T21 lines relative to euploid as well as genes and pathways in NPCs that showed inter-individual variability.
2024-11-06 | GSE273850 | GEO
Project description:We modeled human Trisomy 21 primitive hematopoiesis using induced pluripotent stem cells (iPSCs). Primitive multipotent progenitor populations generated from Trisomy 21 iPSCs showed normal proliferative capacity and megakaryocyte production, enhanced erythropoiesis and reduced myeloid development compared to euploid iPSCs.
2012-09-24 | GSE35561 | GEO
Project description:We modeled human Trisomy 21 primitive hematopoiesis using induced pluripotent stem cells (iPSCs). Primitive multipotent progenitor populations generated from Trisomy 21 iPSCs showed normal proliferative capacity and megakaryocyte production, enhanced erythropoiesis and reduced myeloid development compared to euploid iPSCs. CD41+/235+ iPSC-derived progenitor cells were flow cytometrically sorted for RNA extraction and hybridization onto Affymetrix microarrays.
2012-09-24 | E-GEOD-35561 | biostudies-arrayexpress
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:Children with trisomy 21 (T21) are highly predisposed to acute myeloid leukemia, which is preceded by a pre-leukemic transient abnormal myelopoiesis driven by truncating mutations in GATA1 (GATA1s). We investigated gene expression profiles in T21 and isogenic euploid hematopoietic progenitor cells (HPCs) derived from human induced pluripotent stem cells (iPSCs), in combination GATA1s and STAG2 mutations associated with T21 myeloid leukemia. We identified upregulation of interferon alpha/gamma responses and ribosome subunit pathways in gene set enrichment analysis in T21 versus euploid CD45+ hematopoietic cells, whereas pathways regulating genome integrity including mitotic spindle and G2/M checkpoint were downregulated. GATA1s in T21 cells led to downregulation of heme metabolism and apoptosis pathways as well as a further significant increase in the average expression of genes on chromosome 21. These results suggest that T21 and GATA1s mutations cooperate to disrupt normal HPC functions and cause myeloid lineage skewing.
2024-01-29 | GSE238115 | GEO
Project description:We generated human induced pluripotent stem cells (iPSCs) from trisomy 21 (T21) and euploid patient tissues with and without GATA1 mutations causing exclusive expression of truncated GATA1, termed GATA1short (GATA1s). Transcriptome analysis comparing expression levels of genes in GATA1s vs. wtGATA1-expressing progenitors demonstrated that GATA1s impairs erythropoiesis and enhances megakaryopoiesis and myelopoiesis in both T21 and euploid contexts in the iPSC-model system.
2015-01-26 | GSE36787 | 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:Down syndrome (DS) is caused by an extra copy of chromosome 21. We are characterizing protein changes in human skin fibroblasts. We propose to study corresponding changes at the DNA level (by SNP analysis) and the RNA level (using Affymetrix chips). These studies will detail transcriptional and translational regulation in trisomy. The Specific Aim is to obtain data on RNA transcript levels using Affymetrix expression arrays in a group of trisomy 21 and euploid fibroblast cell lines. In parallel, we will acquire SNP data to determine both genotype (call) and copy number changes for trisomic samples. The results will allow us to identify the patterns of change in a trisomic chromosome (relative to control). [1] We hypothesize that in genomic DNA samples derived from trisomy 21 (TS21) fibroblasts there will be an increased copy number on chr21 with additional microdeletions and microdeletions. [2] We hypothesize that the RNA transcripts derived from chr21 will be elevated relative to euploid controls. [3] We hypothesize that altered RNA transcript levels will be significantly correlated with altered protein levels from these same fibroblast cell lines. The experimental design is as follows. All samples are from deidentified individuals and were obtained from the Brain and Tissue Bank for Developmental Disorders at the University of Maryland, with Johns Hopkins IRB approval.[1] There are five trisomy 21 samples and five euploid samples (total n=10). Fibroblasts were grown in culture to comparable confluency and passage number. Cells were harvested. Total RNA was isolated with a Qiagen kit. The quantity and purity of the RNA was confirmed by spectrophotometry and by electrophoresing an aliquot on a 1% agarose gel. Approximately 10 micrograms of total RNA will be sent to TGen on dry ice for analysis on Affymetrix U133 PlusTwo arrays. Data analysis will be with Affymetrix and Partek software. Keywords: other
2007-12-04 | GSE9762 | GEO
Project description:We generated human induced pluripotent stem cells (iPSCs) from trisomy 21 (T21) and euploid patient tissues with and without GATA1 mutations causing exclusive expression of truncated GATA1, termed GATA1short (GATA1s). Transcriptome analysis comparing expression levels of genes in GATA1s vs. wtGATA1-expressing progenitors demonstrated that GATA1s impairs erythropoiesis and enhances megakaryopoiesis and myelopoiesis in both T21 and euploid contexts in the iPSC-model system. We analyzed the transcriptome of (i) T21 iPSC-derived heamtopoietic progenitors expressing wtGATA1 (6 replicates) or GATA1s (3 replicates), as well as of (ii) euploid iPSC-derived progenitors expressing wtGATA1 (2 replicates) or GATA1s (2 replicates).
2015-01-26 | E-GEOD-36787 | biostudies-arrayexpress
Project description:Down syndrome (DS) is caused by an extra copy of chromosome 21. We are characterizing protein changes in human skin fibroblasts. We propose to study corresponding changes at the DNA level (by SNP analysis) and the RNA level (using Affymetrix chips). These studies will detail transcriptional and translational regulation in trisomy. The Specific Aim is to obtain data on RNA transcript levels using Affymetrix expression arrays in a group of trisomy 21 and euploid fibroblast cell lines. In parallel, we will acquire SNP data to determine both genotype (call) and copy number changes for trisomic samples. The results will allow us to identify the patterns of change in a trisomic chromosome (relative to control). [1] We hypothesize that in genomic DNA samples derived from trisomy 21 (TS21) fibroblasts there will be an increased copy number on chr21 with additional microdeletions and microdeletions. [2] We hypothesize that the RNA transcripts derived from chr21 will be elevated relative to euploid controls. [3] We hypothesize that altered RNA transcript levels will be significantly correlated with altered protein levels from these same fibroblast cell lines. The experimental design is as follows. All samples are from deidentified individuals and were obtained from the Brain and Tissue Bank for Developmental Disorders at the University of Maryland, with Johns Hopkins IRB approval.[1] There are five trisomy 21 samples and five euploid samples (total n=10). Fibroblasts were grown in culture to comparable confluency and passage number. Cells were harvested. Total RNA was isolated with a Qiagen kit. The quantity and purity of the RNA was confirmed by spectrophotometry and by electrophoresing an aliquot on a 1% agarose gel. Approximately 10 micrograms of total RNA will be sent to TGen on dry ice for analysis on Affymetrix U133 PlusTwo arrays. Data analysis will be with Affymetrix and Partek software.
2008-06-16 | E-GEOD-9762 | biostudies-arrayexpress