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Project description:Human iPSC-derived neural stem/progenitor cells (hiPSC-NSCs) are a promising source for cell/gene therapy approaches to target neurodegenerative and demyelinating disorders with unmet clinical needs. Despite the great effort in characterizing hiPSC-derived products in both in vitro and in vivo settings, we still lack a comprehensive study addressing hiPSC-NSC identity and safety at genome-wide level, an issue of paramount importance to establish accepted criteria for prospective clinical applications. Here, we evaluated the transcriptional (by poly-A+ RNA-seq) and epigenetic (by H3K27Ac ChIP-seq) signatures in hiPSCs and differentiated hiPSC-NSC progeny, keeping as reference a somatic clinically relevant human fetal NSC (hfNSCs) line. Overall, our comprehensive transcriptomic and epigenomic analysis coupled to a long-term functional in vivo characterization provided insight into the cell identity, safety profile, and therapeutic potential of hiPSC-NSCs, supporting the rationale for the continuous development of hiPSC-NSCs as an alternative source to somatic hfNSCs for treatment of neurodegenerative and demyelinating disorders.
2024-09-23 | GSE239443 | GEO
Project description:Human iPSC-derived neural stem/progenitor cells (hiPSC-NSCs) are a promising source for cell/gene therapy approaches to target neurodegenerative and demyelinating disorders with unmet clinical needs. Despite the great effort in characterizing hiPSC-derived products in both in vitro and in vivo settings, we still lack a comprehensive study addressing hiPSC-NSC identity and safety at genome-wide level, an issue of paramount importance to establish accepted criteria for prospective clinical applications. Here, we evaluated the transcriptional (by poly-A+ RNA-seq) and epigenetic (by H3K27Ac ChIP-seq) signatures in hiPSCs and differentiated hiPSC-NSC progeny, keeping as reference a somatic clinically relevant human fetal NSC (hfNSCs) line. Overall, our comprehensive transcriptomic and epigenomic analysis coupled to a long-term functional in vivo characterization provided insight into the cell identity, safety profile, and therapeutic potential of hiPSC-NSCs, supporting the rationale for the continuous development of hiPSC-NSCs as an alternative source to somatic hfNSCs for treatment of neurodegenerative and demyelinating disorders.
2024-09-23 | GSE239444 | GEO
Project description:BackgroundGloboid cell leukodystrophy (GLD) is a devastating neurodegenerative disease characterized by widespread demyelination caused by galactocerebrosidase defects. Changes in GLD pathogenesis occurring at the molecular level have been poorly studied in human-derived neural cells. Patient-derived induced pluripotent stem cells (iPSCs) are a novel disease model for studying disease mechanisms and allow the generation of patient-derived neuronal cells in a dish.ResultsIn this study, we identified gene-expression changes in iPSCs and iPSC-derived neural stem cells (NSCs) from a patient with GLD (K-iPSCs/NSCs) and normal control (AF-iPSCs/NSCs), in order to investigate the potential mechanism underlying GLD pathogenesis. We identified 194 (K-iPSCs vs. AF-iPSCs) and 702 (K-NSCs vs. AF-NSCs) significantly dysregulated mRNAs when comparing the indicated groups. We also identified dozens of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway terms that were enriched for the differentially expressed genes. Among them, 25 differentially expressed genes identified by RNA-sequencing analysis were validated using real-time quantitative polymerase chain reaction analysis. Dozens of pathways involved in neuroactive ligand-receptor interactions, synaptic vesicle cycle signaling, serotonergic synapse signaling, phosphatidylinositol-protein kinase B signaling, and cyclic AMP signaling were identified as potential contributors to GLD pathogenesis.ConclusionsOur results correspond to the fact that mutations in the galactosylceramidase gene may disrupt the identified signaling pathways during neural development, suggesting that alterations in signaling pathways contribute to GLD pathogenesis. At the same time, our results demonstrates that the model based on K-iPSCs is a novel tool that can be used to study the underlying molecular basis of GLD.
| S-EPMC10116706 | biostudies-literature
Project description:RNA-seq and ChIP-seq profiling of human iPSCs, derived NSCs and human fetal NSCs
| PRJNA999314 | ENA
Project description:RNA-seq and ChIP-seq profiling of human iPSCs, derived NSCs and human fetal NSCs (ChIP-Seq)
| PRJNA999317 | ENA
Project description:RNA-seq and ChIP-seq profiling of human iPSCs, derived NSCs and human fetal NSCs (RNA-Seq)
| PRJNA999318 | ENA
Project description:Chromatin immunoprecipitation (ChIP)-seq analyses of transcription factors in clinical specimens are challenging due to the technical limitations and low quantities of starting material, often resulting in low enrichments and poor signal-to-noise ratio. Here, we present an optimized protocol for transcription factor ChIP-seq analyses in human tissue, yielding an ?100% success rate for all transcription factors analyzed. As proof of concept and to illustrate general applicability of the approach, human tissue from the breast, prostate, and endometrial cancers were analyzed. In addition to standard formaldehyde fixation, disuccinimidyl glutarate was included in the procedure, greatly increasing data quality. To illustrate the sensitivity of the optimized protocol, we provide high-quality ChIP-seq data for three independent factors (AR, FOXA1, and H3K27ac) from a single core needle prostate cancer biopsy specimen. In summary, double-cross-linking strongly improved transcription factor ChIP-seq quality on human tumor samples, further facilitating and enhancing translational research on limited amounts of tissue.
| S-EPMC6311467 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-30 | E-GEOD-57358 | biostudies-arrayexpress
Project description:The human K562 chronic myeloid leukemia cell line has long served as an experimental paradigm for functional genomic studies. To systematically and functionally annotate the human genome, the ENCODE consortium generated hundreds of functional genomic data sets, such as chromatin immunoprecipitation coupled to sequencing (ChIP-seq). While ChIP-seq analyses have provided tremendous insights into gene regulation, spatiotemporal insights were limited by a resolution of several hundred base pairs. ChIP-exonuclease (ChIP-exo) is a refined version of ChIP-seq that overcomes this limitation by providing higher precision mapping of protein-DNA interactions. To study the interplay of transcription initiation and chromatin, we profiled the genome-wide locations for RNA polymerase II (Pol II), the histone variant H2A.Z, and the histone modification H3K4me3 using ChIP-seq and ChIP-exo. In this Data Descriptor, we present detailed information on parallel experimental design, data generation, quality control analysis, and data validation. We discuss how these data lay the foundation for future analysis to understand the relationship between the occupancy of Pol II and nucleosome positions at near base pair resolution.
| S-EPMC5839155 | biostudies-literature
Project description:Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by electron microscopy revealed the presence of lipid and glycogen storage, tight junctions and bile canaliculi- all typical features of hepatocytes. Furthermore, the transcriptome of undifferentiated E-iPSC, DE, HE and HLCs were compared to that of fetal liver and primary human hepatocytes (PHH). K-means clustering identified 100 clusters which include developmental stage-specific groups of genes, e.g. OCT4 expression at the undifferentiated stage, SOX17 marking the DE stage, DLK and HNF6 the HE stage, HNF4α and Albumin is specific to HLCs, fetal liver and adult liver (PHH) stage. We use E-iPSCs for modeling gene regulatory networks associated with human hepatogenesis and gastrulation in general.
| S-EPMC5524812 | biostudies-literature