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Series GSE99843 Query DataSets for GSE99843
Status Public on Jun 10, 2017
Title Progressive motor neuron pathology and the role of astrocytes in a human stem cell model of VCP-related ALS [terminally differentiated iPSC-derived astrocytes]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Motor neurons (MNs) and astrocytes (ACs) are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but their interaction and the sequence of molecular events leading to MN death remain unresolved. Herewe optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (>85%) functional populations of spinal cord MNs and ACs. We identifysignificantlyincreased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP)-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. Cumulatively these cellular stresses result in synaptic pathology and cell death in VCP-mutant MNs. We additionallyidentify a cell-autonomous VCP-mutant AC survival phenotype, which is not attributable to the same molecular pathology occurring in VCP-mutant MNs. Finally, through iterative co-culture experiments, we uncover non-cell-autonomous effects of VCP-mutant ACs on both control and mutant MNs. This work elucidates molecular events and cellular interplay thatcould guide future therapeutic strategies in ALS.
Overall design Bulk RNA-seq at different timepoints throughout a 35-day differentiation protocol that converted iPSC cells to highly enriched motor neurons and a further dataset from terminally differentiated iPSC-derived astrocytes
Contributor(s) Hall C, Yao Z, Choi M, Tyzack G, Serio A, Luisier R, Harley J, Preza E, Arber C, Crisp SJ, Watson PM, Kullmann DM, Abramov A, Wray S, Burley R, Loh SH, Martins ML, Stevens MM, Luscombe N, Sibley C, Lakatos A, Ule J, Gandhi S, Patani R
Citation(s) 28564594, 29789581
Submission date Jun 09, 2017
Last update date Jul 25, 2021
Contact name Raphaelle Luisier
Phone 0041762432198
Organization name Idiap Research Institute
Lab Genomics and Health Informatics
Street address Rue Marconi 19, PO Box 592
City Martigny
State/province Valais
ZIP/Postal code 1920
Country Switzerland
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (4)
GSM2654096 Sample 32 [CTRL 4 wks]
GSM2654097 Sample 33 [CTRL 4 wks]
GSM2654098 Sample 34 [CTRL 4 wks]
This SubSeries is part of SuperSeries:
GSE98290 Post-transcriptional remodelling is temporally deregulated during motor neurogenesis in human ALS models
BioProject PRJNA389775
SRA SRP108875

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE99843_RAW.tar 8.0 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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