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FUS H517Q and healthy iPSC-derived motor neurons

ABSTRACT: FUS H517Q and healthy iPSC-derived motor neurons

PROVIDER: PRJNA838945 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19241816_1.fastq.gz	Fastqsanger.gz
	SRR19241816_2.fastq.gz	Fastqsanger.gz
	SRR19241817.fastq.gz	Fastqsanger.gz
	SRR19241818_1.fastq.gz	Fastqsanger.gz
	SRR19241818_2.fastq.gz	Fastqsanger.gz

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Small RNA-sequencing of FUS H517Q and healthy iPSC-derived motor neurons

Project description:We sought to investigate changes in expression levels of small RNAs including microRNAs in FUS H517Q and healthy motor neurons Motor neurons were differentiated from patient-derived FUS H517Q and healthy iPSCs, and harvested at day 30. We performed gene expression profiling analysis using data obtained from bulk small RNA-seq.

2022-05-20 | GSE203170 | GEO

Bulk RNA-sequencing of FUS H517Q and healthy iPSC-derived motor neurons

Project description:We sought to investigate changes in gene expression levels including changes in pri-microRNAs in FUS H517Q motor neurons Motor neurons were differentiated from patient-derived FUS H517Q and healthy iPSCs, and harvested at day 30. We performed gene expression profiling analysis using data obtained from bulk RNA-seq.

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Bulk RNA-sequencing of FUS H517Q and healthy iPSC-derived motor neurons

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Small RNA-sequencing of FUS H517Q and healthy iPSC-derived motor neurons

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HTA2.0 (human transcriptome array) analysis of control iPSC-derived motor neurons (MN), FUS-H517D-hetero-iPSC-MN, and FUS-H517D-homo-iPSC-MNs

Project description:To assess RNA regulation in the MN possessing mutated FUS-H517D gene. Fused in sarcoma/translated in liposarcoma (FUS) is a causative gene of familial amyotrophic lateral sclerosis (fALS). Mutated FUS causes accumulation of DNA damage stress and stress granule (SG) formation, etc., thereby motor neuron (MN) death. However, key molecular etiology of mutated FUS-dependent fALS (fALS-FUS) remains unclear. Here, Bayesian gene regulatory networks (GRN) calculated by Super-Computer with transcriptome data sets of induced pluripotent stem cell (iPSC)-derived MNs possessing mutated FUSH517D (FUSH517D MNs) and FUSWT identified TIMELESS, PRKDC and miR-125b-5p as "hub genes" which influence fALS-FUS GRNs. miR-125b-5p expression up-regulated in FUSH517D MNs, showed opposite correlations against FUS and TIMELESS mRNA levels as well as reported targets of miR-125b-5p. In addition, ectopic introduction of miR-125b-5p could suppress mRNA expression levels of FUS and TIMELESS in the cells. Furthermore, we found TIMELESS and PRKDC among key players of DNA damage stress response (DDR) were down-regulated in FUSH517D MNs and cellular model analysis validated DDR under impaired DNA-PK activity promoted cytosolic FUS mis-localization to SGs. Our GRNs based on iPSC models would reflect fALS-FUS molecular etiology.

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Gene expression from human iPSC derived motor neurons.

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Project description:To clarify the functional properties of FUS, we established the differentially expressed alternative exons in FUS-silenced primary motor neurons by using exon-sensitive microarray technology. To clarify the functional properties of FUS, we established the differentially expressed alternative exons in FUS-silenced primary glial cells by using exon-sensitive microarray technology. To clarify the functional properties of FUS, we established the differentially expressed alternative exons in FUS-silenced primary cerebellar neurons by using exon-sensitive microarray technology.

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