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Stem cell derived spinal cord chips reproduce disease biomarkers in sporadic ALS patients [snRNAseq]

ABSTRACT: Stem cell derived spinal cord chips reproduce disease biomarkers in sporadic ALS patients [snRNAseq]

PROVIDER: PRJNA1075765 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR27965900.fastq.gz	Fastqsanger.gz
	SRR27965902.fastq.gz	Fastqsanger.gz
	SRR27965903.fastq.gz	Fastqsanger.gz
	SRR27965905.fastq.gz	Fastqsanger.gz

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Stem cell derived spinal cord chips reproduce disease biomarkers in sporadic ALS patients [snRNAseq]

Project description:Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder with complex origins. Familial monogenetic causes of ALS make up a small percentage of patients overall, and the cause of the majority of idiopathic (sporadic) form remains unknown. Frequently utilized for disease modeling, human induced pluripotent stem cell (iPSC)-derived motor neuron cultures lack cellular maturity in vitro and rarely recapitulate clinically relevant phenotypes of ALS. Microfluidic organ-on-chip systems enable co-culture of multiple disease-relevant cell types and enhance cellular maturity. Here, we describe the generation of spinal cord (SC)-chips from 8 sporadic ALS (sALS) patients and 10 non-diseased controls. Transcriptomic and proteomic analyses of SC-Chips revealed changes in expression of targets known to be disrupted in ALS patients. Particularly, intermediate filaments (IF) neurofilament heavy (NEFH), medium (NEFM), and light (NEFL) were upregulated in SC-Chips from sALS patients. Single nuclei RNAseq (sNucseq) of SC-Chips revealed two subpopulations of motor neurons and cell-specific changes related to ALS pathogenesis and mimicking conditions in vivo.

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Stem cell derived spinal cord chips reproduce disease biomarkers in sporadic ALS patients [bulk RNAseq]

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Stem cell derived spinal cord chips reproduce disease biomarkers in sporadic ALS patients [bulk RNAseq]

Project description:Stem cell derived spinal cord chips reproduce disease biomarkers in sporadic ALS patients [bulk RNAseq]

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Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls.

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Project description:Differentiated motor neurons from hiPSC derived from peripheral nerve fibroblasts of sporadic ALS patients and evaluated the gene expression profile by means microarray-linked to specific analysis tools. Two-condition experiment, ALS patients motor neurons vs. controls. Biological replicates: 3 ALS replicates, 3 control replicates.

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Distinct brain transcriptome profiles in c9orf72-associated and sporadic ALS

Project description:Increasing evidence suggests that defective RNA processing contributes to the development of amyotrophic lateral sclerosis (ALS). This may be especially true for ALS caused by a repeat expansion in C9orf72 (c9ALS), in which the accumulation of RNA foci and dipeptide-repeat proteins are expected to modify RNA metabolism. We report extensive alternative splicing (AS) and alternative polyadenylation (APA) defects in the cerebellum of c9ALS cases (8,224 AS, 1,437 APA), including changes in ALS-associated genes (e.g. ATXN2 and FUS), and cases of sporadic ALS (sALS; 2,229 AS, 716 APA). Furthermore, hnRNPH and other RNA-binding proteins are predicted as potential regulators of cassette exon AS events for both c9ALS and sALS. Co-expression and gene-association network analyses of gene expression and AS data revealed divergent pathways associated with c9ALS and sALS. Examination transcriptiome profiles in c9orf72-associated ALS, sporadic ALS and healthy control

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