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Identifying Altered Developmental Pathways in Induced Pluripotent Stem Cell-Derived Neural Stem Cells From a Patients with Globoid Cell Leukodystrophy Using Transcriptome Profiling

ABSTRACT: Identifying Altered Developmental Pathways in Induced Pluripotent Stem Cell-Derived Neural Stem Cells From a Patients with Globoid Cell Leukodystrophy Using Transcriptome Profiling

PROVIDER: PRJNA875679 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21387322_1.fastq.gz	Fastqsanger.gz
	SRR21387322_2.fastq.gz	Fastqsanger.gz
	SRR21387323_1.fastq.gz	Fastqsanger.gz
	SRR21387323_2.fastq.gz	Fastqsanger.gz
	SRR21387324_1.fastq.gz	Fastqsanger.gz

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Identifying altered developmental pathways in human globoid cell leukodystrophy iPSCs-derived NSCs using transcriptome profiling.

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.

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Identifying Altered Developmental Pathways in Induced Pluripotent Stem Cell-Derived Neural Stem Cells From a Patients with Globoid Cell Leukodystrophy Using Transcriptome Profiling

Project description:we identified gene-expression changes in induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells (NSCs) from a patients 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.

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