% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@MISC{Karmali:285262,
author = {Karmali, Nasser},
title = {{D}ataset: {S}ingle-cell transcriptomic changes in
oligodendroglial lineage cells derived from {P}arkinson’s
disease patient-i{PSC}s with {LRRK}2-{G}2019{S} mutation
({S}eries {GSE}277350)},
publisher = {Gene Expression Omnibus},
reportid = {DZNE-2026-00204},
year = {2026},
abstract = {Despite 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.},
cin = {AG Heutink},
cid = {I:(DE-2719)1210002},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)32},
url = {https://pub.dzne.de/record/285262},
}