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Transcriptome analysis of neural progenitor cells derived from Lowe Syndrome induced pluripotent stem cells

ABSTRACT: Transcriptome analysis of neural progenitor cells derived from Lowe Syndrome induced pluripotent stem cells

PROVIDER: PRJNA530789 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8844640_1.fastq.gz	Fastqsanger.gz
	SRR8844640_2.fastq.gz	Fastqsanger.gz
	SRR8844641_1.fastq.gz	Fastqsanger.gz
	SRR8844641_2.fastq.gz	Fastqsanger.gz
	SRR8844642_1.fastq.gz	Fastqsanger.gz

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Transcriptome analysis of neural progenitor cells derived from Lowe Syndrome induced pluripotent stem cells

Project description:Lowe Syndrome (LS) is caused by loss-of-function mutations in the X-linked gene OCRL that codes for a 901 amino acid protein, inositol polyphosphate 5-phosphatase, which plays a key role in endosome recycling, clathrin coated pit formation and actin polymerization. It is characterized by congenital cataracts, intellectual and developmental disability, and renal proximal tubular dysfunction. Patients are also at high risk for developing glaucoma and seizures. We recently developed induced pluripotent stem cells (iPSCs) from three patients with LS who have hypomorphic variants affected the 3’ end of the gene, and their neurotypical brothers to serve as controls. In this study, we used RNA sequencing (RNA-seq) to obtain a transcriptome profile in neural progenitor cells (NPCs). Thirty-six differentially expressed genes (DEGs) were found in patient/control comparisons that were shared across all three sets of sibling pairs. Interestingly, two-thirds of these genes have previously been found to be involved in neuropsychiatric and neurodevelopmental disorders. Furthermore, 14 of the DEGs are strong candidate genes for a variety of eye disorders, including glaucoma development. The most notable example is EFEMP1, which was significantly increased in LS NPCs. These DEGs found in NPCs could reflect similar alterations occurring in eye tissues or their progenitor cells from LS. Overall, the RNA-seq findings present several molecular pathways that could explain the underlying basis for the neurodevelopmental and eye problems seen in boys with LS.

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Overexpression of Lin28A in neural progenitor cells in vivo does not lead to brain tumor formation but results in reduced spine density

Project description:The RNA binding protein LIN28A is a stem- and progenitor marker and one of the factors necessary to induce pluripotent stem cells in vitro. LIN28A has been shown to promote the proliferative capacity of neural progenitor cells but its specific role during embryonal and postnatal brain development still remains widely unknown. A high and characteristic overexpression of LIN28A has been identified in malignant brain tumors called embryonal tumors with multilayered rosettes (ETMR). Radial glia cells of the ventricular zone are proposed as a cell of origin for those tumors.

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Enabling phenotypic drug discovery for neurological mitochondrial DNA disorders with patient-derived neural progenitor cells

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