Homo sapiens
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PROVIDER: PRJNA308728 | ENA |
REPOSITORIES: ENA
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Project description:Functional neurons generated from T cell-derived iPSCs for neurological disease modeling
| PRJNA308724 | ENA
Project description:Induced pluripotent stem cells (iPSCs) harbor great promise for in vitro generation of disease-relevant cell types, such as mesodiencephalic dopaminergic (mdDA) neurons involved in Parkinson’s disease. Although iPSC-derived midbrain DA neurons have been generated, detailed genetic and epigenetic characterization of such neurons is still lacking. The goal of this study is to examine the authenticity of iPSC-derived DA neurons obtained by established protocols. We FACS-purified mdDA (Pitx3gfp/+) neurons derived from mouse iPSCs and primary mdDA (Pitx3gfp/+) neurons to analyze and compare their genetic and epigenetic features. Although iPSC-derived DA neurons largely adopt characteristics of their in-vivo counterparts, relevant deviations in global gene expression and DNA methylation were found. Hypermethylated genes, mainly involved in neurodevelopment and basic neuronal functions, consequently showed reduced expression levels. Such abnormalities should be addressed as they might affect unambiguous long-term functionality and hamper the potential of iPSC-derived DA neurons for in-vitro disease modeling or cell-based therapy. RRBS methylation maps were generated for iPSCs cells, dopaminergic neurons derived from iPSCs and primary mesodiencephalic dopaminergic neurons
2014-03-01 | E-GEOD-55475 | biostudies-arrayexpress
Project description:In this study, we investigated its suitability for disease modeling by carrying out gene expression profiling, using RNA-seq, on neurons derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs) and fibroblasts (F-iPSCs). Comparison of expression profiles of iPSC derived from dental pulp and skin-fibroblast
2013-05-01 | E-GEOD-43143 | biostudies-arrayexpress
Project description:In this study, we investigated its suitability for disease modeling by carrying out gene expression profiling, using RNA-seq, on neurons derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs) and fibroblasts (F-iPSCs).
2014-01-01 | GSE43143 | GEO
Project description:NGN2-driven iPSC-to-neuron conversion is a popular method for human neurological disease modeling. In this study, we report a fully standardized approach for generating functional excitatory cortical neurons. This method utilizes clonal, targeted-engineered iPSC lines and employs fully defined reagents. We demonstrate that our protocol generates consistent excitatory cortical neurons at scale. Comprehensive temporal omics, electrophysiological, and morphological profilings indicate the continued progression of neuronal maturation for at least 150 days. Deep quantitative characterizations through transcriptomic, imaging, and functional assays reveal coordinated actions of multiple pathways driving neuronal maturation. The neurons express the majority of the key risk genes in Alzheimer's disease, Parkinson's disease, and autism, demonstrating the relevance of our protocol in modeling human neurological disorders. This well-defined method, profiling data, and functional characterization provide a solid and reliable framework for developing human in vitro neuronal models for disease modeling.
2023-10-18 | MSV000093150 | MassIVE
Project description:Induced Pluripotent Stem Cells (iPSC) derived from healthy individuals are important controls for disease modeling studies. To create a resource of genetically annotated iPSCs, we reprogrammed footprint-free lines from four volunteers in the Personal Genome Project Canada (PGPC). Multilineage directed differentiation efficiently produced functional cortical neurons, cardiomyocytes and hepatocytes. Pilot users further demonstrated line versatility by generating kidney organoids, T-lymphocytes and sensory neurons. A frameshift knockout was introduced into MYBPC3 and these cardiomyocytes exhibited the expected hypertrophic phenotype. Whole genome sequencing (WGS) based annotation of PGPC lines revealed on average 20 coding variants. Importantly, nearly all annotated PGPC and HipSci lines harboured at least one pre-existing or acquired variant with cardiac, neurological or other disease associations. Overall, PGPC lines were efficiently differentiated by multiple users into cell types found in six tissues for disease modeling, and clinical annotation highlighted variant-preferred lines for use as unaffected controls in specific disease settings.
2019-10-03 | GSE132012 | GEO
Project description:Induced pluripotent stem cells (iPSCs) hold great promise for in vitro disease modeling and cell replacement therapy for Parkinson’s disease (PD). Both applications crucially require an in-depth profiling of the disease-relevant, iPSC-derived cell type. Midbrain dopaminergic (mDA) neurons derived from pluripotent stem cells are of substantial interest because of their instrumental value for PD therapy. IPSC-derived mDA neuron-like cells have been generated, however, detailed genetic and epigenetic characterization of strictly purified in vitro generated DA neurons has so far lagged behind. We generated mouse Pitx3gfp/+ iPSC-derived DA neurons that, after fluorescent activated cell sorting (FACS) allowed comprehensive comparison to mesodiencephalic dopaminergic (mdDA) neurons from Fac-sorted Pitx3gfp/+ ventral midbrains. We performed detailed analysis of global gene expression and genome-scale DNA methylation of CpG islands (CGIs) by reduced representation bisulfite sequencing. The reprogramming pathway from fibroblasts to iPSCs left parental cell footprints for both gene expression and DNA methylation. However, most gene expression patterns of iPSC-derived DA neurons closely resembled that of primary mdDA neurons with the strongest correlations for mdDA specific genes. Also, for DNA methylation patterns, high similarities were found for the vast majority of CGIs when comparing primary mdDA neurons with iPSC-derived DA neurons. Additionally, we found de novo DNA methylation during in vitro differentiation for hundreds of genes specifically in lineage-committed neural precursors that persisted in iPSC-derived DA neurons. Our study provides novel detailed characteristics of iPSC-derived DA neurons in comparison to the primary cell type. These findings add important information to our knowledge about these biomedically highly valuable, in vitro generated neurons. Microarray expression study comparing 3 samples of facs-sorted, Pitx3-gfp positive cells from each experimental group to a common reference consisting of adult mouse midbrain RNA. Each sample was analysed in normal and opposite dye orientation.
2014-05-13 | E-GEOD-47178 | biostudies-arrayexpress
Project description:Induced pluripotent stem cells (iPSCs) harbor great promise for in vitro generation of disease-relevant cell types, such as mesodiencephalic dopaminergic (mdDA) neurons involved in Parkinson’s disease. Although iPSC-derived midbrain DA neurons have been generated, detailed genetic and epigenetic characterization of such neurons is still lacking. The goal of this study is to examine the authenticity of iPSC-derived DA neurons obtained by established protocols. We FACS-purified mdDA (Pitx3gfp/+) neurons derived from mouse iPSCs and primary mdDA (Pitx3gfp/+) neurons to analyze and compare their genetic and epigenetic features. Although iPSC-derived DA neurons largely adopt characteristics of their in-vivo counterparts, relevant deviations in global gene expression and DNA methylation were found. Hypermethylated genes, mainly involved in neurodevelopment and basic neuronal functions, consequently showed reduced expression levels. Such abnormalities should be addressed as they might affect unambiguous long-term functionality and hamper the potential of iPSC-derived DA neurons for in-vitro disease modeling or cell-based therapy.
2014-03-01 | GSE55475 | GEO
Project description:The differentiation of patient-specific induced pluripotent stem cells (iPSCs) into specific neuronal subtypes has been exploited as an approach to modeling a variety of neurological disorders. However, achieving a highly pure population of neurons is challenging when using directed differentiation methods, especially for neuronal subtypes generated by complex and protracted protocols. In this study, we efficiently produced highly pure populations of regionally specified CNS neurons by using a modified NGN2-Puromycin direct conversion protocol. The protocol is amenable across a range of iPSC lines, with an efficiency above 97% by day 21, and above 95% of neurons positive for MAP2. This NGN2-Puromycin conversion resulted in a significant number of peripheral neurons, but by incorporating a short CNS patterning step, we eliminated these peripheral neurons. Furthermore, we used the patterning step to control the rostral-caudal identity. This approach to sequential patterning and NGN2-Puromycin conversion, when patterned with SMAD inhibitors, produced pure populations of forebrain neurons; when SMAD inhibitors and WNT agonists were applied, the approach produced anterior hindbrain excitatory neurons, resulting in a neuronal population containing VSX2/SHOX2 V2a interneurons. Overall, this sequential patterning and conversion protocol can be used for the production of a variety of CNS excitatory neurons from patient-derived iPSCs, which is a highly versatile system for investigating early disease events for a range of neurological disorders including Alzheimer's disease, motor neurons disease and spinal cord injury.
2020-06-24 | GSE149864 | GEO
Project description:In this study we determine the genomic methylation profile by MBD-seq of T cell derived iPSCs and aHDF derived iPSCs.
2016-01-14 | GSE76831 | GEO