Integrated bulk, single-cell, and spatial transcriptomic analyses prioritize NOTCH1 as a candidate gene associated with neurovascular and immune-related alterations in Parkinson's disease.
Overview
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Laboratory Center of Chongqing Medical University, Chongqing, China
- Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, China
- School of Medicine, Chongqing University, Chongqing, China
Abstract
Introduction: Parkinson’s disease (PD) is classically defined by dopaminergic neurodegeneration in the substantia nigra, yet how immune activation is linked to neurovascular dysfunction in the diseased brain remains incompletely understood.
Methods: Here, we integrated bulk substantia nigra microarray expression datasets with single-cell and spatial transcriptomic data to delineate disease-associated neurovascular and immune-related transcriptomic programs in PD.
Results: Across three independent human microarray cohorts, differential expression and weighted gene co-expression network analyses identified PD-associated genes enriched for synaptic processes together with immune, adhesion, and vascular-related pathways. Network topology analysis and machine-learning feature selection prioritized a five-gene candidate panel, among which NOTCH1 showed the most consistent cross-dataset association and external directional support. Importantly, quantitative real-time PCR (qRT-PCR) validation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,
Discussion: Collectively, these analyses prioritize NOTCH1 as a reproducible PD-associated candidate gene and suggest that NOTCH1-related signals may be embedded within broader neurovascular, glial, inflammatory, extracellular-matrix, and immune-associated transcriptomic alterations. These findings provide a computational prioritization framework for future experimental validation rather than evidence of a defined NOTCH-driven mechanism.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE243639, at NCBI GEO; found in the text, “Data sources and preprocessing”
Data availability statement
The datasets analyzed in this study are publicly available in the NCBI GEO repository. The human substantia nigra bulk transcriptomic datasets include GSE20141 (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 5 authors, 5 keywords, 46 references.
Cite
This paper
Li, W., Wei, J., Tan, C., Liu, X., & Chen, L. (2026). Integrated bulk, single-cell, and spatial transcriptomic analyses prioritize NOTCH1 as a candidate gene associated with neurovascular and immune-related alterations in Parkinson's disease. Frontiers in neuroscience, 20, 1862571. https://
BibTeX
@article{li2026integrate
author = {Li, Wenkui and Wei, Jiahao and Tan, Changhong and Liu, Xi and Chen, Lifen},
title = {{Integrated bulk, single-cell, and spatial transcriptomic analyses prioritize NOTCH1 as a candidate gene associated with neurovascular and immune-related alterations in Parkinson's disease}},
journal = {Frontiers in neuroscience},
year = {2026},
month = jul,
volume = {20},
pages = {1862571},
publisher = {Frontiers Media SA},
issn = {1662-4548},
doi = {10.3389/
url = {https://
pmid = {42465723},
pmcid = {PMC13373119}
}
RIS
TY - JOUR
AU - Li, Wenkui
AU - Wei, Jiahao
AU - Tan, Changhong
AU - Liu, Xi
AU - Chen, Lifen
TI - Integrated bulk, single-cell, and spatial transcriptomic analyses prioritize NOTCH1 as a candidate gene associated with neurovascular and immune-related alterations in Parkinson's disease
T2 - Frontiers in neuroscience
J2 - Front Neurosci
PY - 2026
DA - 2026/
VL - 20
SP - 1862571
SN - 1662-4548
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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