000285262 001__ 285262
000285262 005__ 20260219141836.0
000285262 037__ $$aDZNE-2026-00204
000285262 1001_ $$0P:(DE-2719)9002885$$aKarmali, Nasser$$b0$$udzne
000285262 245__ $$aDataset: Single-cell transcriptomic changes in oligodendroglial lineage cells derived from Parkinson’s disease patient-iPSCs with LRRK2-G2019S mutation (Series GSE277350)
000285262 260__ $$bGene Expression Omnibus$$c2026
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000285262 520__ $$aDespite extensive research, the contribution of the LRRK2 p.G2019S mutation to Parkinson's disease (PD) remains unclear. Recent findings indicate oligodendrocytes (ODCs) and their progenitors are vulnerable in PD pathogenesis. Notably, oligodendrocyte precursor cells (OPCs) exhibit high endogenous expression of LRRK2. We induced PD patient-iPSCs with the LRRK2 p.G2019S mutation into oligodendroglial lineages and performed single-cell RNA sequencing. Cell type composition analysis revealed an increase in OPCs, proliferating OPCs and ciliated ependymal cells in LRRK2 lines, all of which are characterized by LRRK2 expression. Differential expression analysis revealed transcriptomic changes in several pathways, including down-regulation of genes related to myelin assembly in ODCs, semaphorin-plexin pathway in OPCs, and cilium movement in proliferating OPCs. Cell-cell communication analysis identified significant alterations in several signaling pathways including a deactivation of PSAP signaling and an activation of MIF signaling in LRRK2 lines. Additionally, we observed an overall increase in SEMA6 signaling communication in LRRK2 cell lines; however, OPCs derived from these LRRK2 lines specifically lost SEMA6 signaling due to a down-regulation of SEMA6A and PLXNA2. Pseudotemporal trajectory analysis revealed that SHH had significantly altered expression along the pseudotime, accompanied by higher expression levels in LRRK2 lines. We propose that dysfunctional semaphorin-plexin signaling, along with cilia movement and SHH signaling, might represent early events in PD pathology.
000285262 536__ $$0G:(DE-HGF)POF4-354$$a354 - Disease Prevention and Healthy Aging (POF4-354)$$cPOF4-354$$fPOF IV$$x0
000285262 8564_ $$uhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE277350
000285262 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002885$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000285262 9131_ $$0G:(DE-HGF)POF4-354$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Prevention and Healthy Aging$$x0
000285262 9201_ $$0I:(DE-2719)1210002$$kAG Heutink$$lGenome Biology of Neurodegenerative Diseases$$x0
000285262 980__ $$adataset
000285262 980__ $$aEDITORS
000285262 980__ $$aVDBINPRINT
000285262 980__ $$aI:(DE-2719)1210002
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