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BioProject

KAP240761

BioProject Title

Single-cell and spatial transcriptomic analysis to elucidate the molecular mechanisms underlying sporadic Parkinson's disease in South Korea

The heterogeneity in various aspects of Parkinson's disease (PD) is increasingly recognized as an important aspect in understanding the condition, with ethnicity and race being one of the major causes of heterogeneity that affects the risk and symptoms of PD onset. While there have been numerous reports related to PD in East Asia, there has been a lack of contribution from single-cell (or nucleus) transcriptome studies, which have been making significant contributions to understanding PD. In this study, we profiled nuclei extracted from the substantia nigra (SN) of confirmed pathological PD and control patients in South Korea, revealing 8 different cell types through cluster analysis. Monocle-based pseudotime analysis identified two disease-associated trajectories for each astrocyte and microglia and identified genes that differentiate them. Interestingly, we uncovered the inflammatory intervention in the early PD-associated transition in microglia and identified the molecular features of this intermediate state of microglia. In addition, gene regulatory networks (GRNs) based on TENET analysis revealed the detrimental effect of an HSPA5-led module in microglia and MSRB3- and HDAC8- led modules specifying the two different astrocyte trajectories. In SN neurons, we observed high heterogeneity and population changes, a decrease in dopaminergic and glutamatergic neurons and a proportional increase in GABAergic neurons. By deconvolution in spatial transcriptome obtained the PD sample, we confirmed spatiotemporal heterogeneity of neuronal subpopulations and PD-associated progressive gliosis specific to dopaminergic nuclei, SN and ventral tegmental areas (VTAs). In conclusion, our approach has enabled us to identify the genetic and spatial characterization of neurons and to demonstrate different glial fates in PD. These findings advance our molecular understanding of cell type-specific changes in Korean PD progression, providing an important foundation for predicting and validating interventions or drug effects for future treatments.

Common Fields

Common Fields - BioProject, Taxonomic type, Organism, Biomaterial provider, Submission date
BioProject	KAP240761
Taxonomic type	Human
Organism	Homo sapiens (9606)
Biomaterial provider	Seoul National University Hospital Brain Bank (SNUH-BB)
Submission date	2024-07-03

Accession

Accession - Submissions
Experiments	All experiments [14]

BioSample [Human]

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BioSample [Human Sample] - BioSample ID, Sample Name, Matadata
BioSample ID	Sample name	Age	Biomaterial provider	Collection Date	Description	Disease	Disease stage	Ethnicity	Geographic location	Health state	Isolate	NCBI taxonomy ID	Organism	Phenotype	Race	Sample type	Sex	Specimen voucher	Tissue	Other characteristics	Registration Date
KAS24117480	SNU17	79	Seoul National University Hospital Brain Bank (SNUH-BB)	2024-04-28	1. Primary age-related tauopathy (PART) 2. LATE-NC	PART	PART	Korean	South Korea	Pancreatic cancer	postmortem, FFPE MB block	9606	Homo sapiens	Thal phase: 0, LB Braak: 0, Tau Braak: 3, CERAD: 0, LATE-NC (TDP-43): 1, CAA: 0, Arteriolosclerosis: 3, Artherosclerosis: Moderate in Circle of Willis, Others: ARTAG (Aging-Related Tau Astrogliopathy)	asian	brain tissue	male	missing	midbrain tissue section	APOE : ɛ3/3	2025-05-21
KAS24117479	SNU16	82	Seoul National University Hospital Brain Bank (SNUH-BB)	2024-04-11	1. Parkinson's disease, Neocortical (Incidental lewy body disease) 2. LATE-NC	PD	PD	Korean	South Korea	Diffuse large B-cell lymphoma, non-GCB subtype	postmortem, FFPE MB block	9606	Homo sapiens	Thal phase: 0, LB Braak: 6, Tau Braak: 3, CERAD: 0, LATE-NC (TDP-43): 1, CAA: 0, Arteriolosclerosis: 2, Artherosclerosis: 0, Others: ARTAG (Aging-Related Tau Astrogliopathy)	asian	brain tissue	male	missing	midbrain tissue section	APOE : ɛ3/3	2025-05-21
KAS24117478	SNU14	78	Seoul National University Hospital Brain Bank (SNUH-BB)	2022-12-01	Parkinson's disease, Brainstem predominant (Incidental lewy body disease)	PD	PD	Korean	South Korea	Colon cancer	postmortem, FFPE MB block	9606	Homo sapiens	Thal phase: 3, LB Braak: 3, Tau Braak: 2, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 2, Artherosclerosis: Mild in basilar artery, Others: Mild loss of Purkinje cells with bergmann's gliosis	asian	brain tissue	female	missing	midbrain tissue section	APOE : ɛ2/3	2025-05-21
KAS24117477	SNU13_Dup	45	Seoul National University Hospital Brain Bank (SNUH-BB)	2022-07-27	Parkinson's disease, Neocortical	PD	PD	Korean	South Korea	Parkinson's disease	postmortem, FFPE MB block	9606	Homo sapiens	Thal phase: 1, LB Braak: 6, Tau Braak: 2, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 0, Artherosclerosis: 0, Others: Concentric sclerosis of vascular wall, perivascular dilatation, microbeeding and hemosiderin-laden macrophage infiltration, perivascualr rarefaction of the myelinated nerve fibers and perivascular deposit of corpora amylacea, PARK2 exon2-4 deletion	asian	brain tissue	male	missing	midbrain tissue section	APOE : ɛ3/4	2025-05-13
KAS24091971	SNU13	45	Seoul National University Hospital Brain Bank (SNUH-BB)	2022-07-27	Parkinson's disease, Neocortical	PD	PD	Korean	South Korea	Parkinson's disease	postmortem, FFPE MB block	9606	Homo sapiens	Thal phase: 1, LB Braak: 6, Tau Braak: 2, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 0, Artherosclerosis: 0, Others: Concentric sclerosis of vascular wall, perivascular dilatation, microbeeding and hemosiderin-laden macrophage infiltration, perivascualr rarefaction of the myelinated nerve fibers and perivascular deposit of corpora amylacea, PARK2 exon2-4 deletion	asian	brain tissue	male	SNUH-BB : BB2211	midbrain tissue section	APOE : ɛ3/4	2024-06-27
KAS24091970	SNU12	61	Seoul National University Hospital Brain Bank (SNUH-BB)	2019-03-10	Primary age-related tauopathy	PART	PART	Korean	South Korea	Gastric cancer	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 1, LB Braak: 0, Tau Braak: 1, CERAD: 1, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 0, Artherosclerosis: Mild atherosclerosis of circle of Willis.	asian	brain tissue	male	SNUH-BB : BB1905	midbrain tissue, substantia nigra	APOE : ɛ3/3	2024-06-27
KAS24091969	SNU11	74	Seoul National University Hospital Brain Bank (SNUH-BB)	2018-08-04	Parkinson's disease, limbic	PD	PD	Korean	South Korea	Parkinson's disease	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 0, LB Braak: 5, Tau Braak: 1, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 0, Artherosclerosis: Mild in circle of willis.	asian	brain tissue	female	SNUH-BB : BB1810	midbrain tissue, substantia nigra	APOE : ɛ3/3	2024-06-27
KAS24091968	SNU10	61	Seoul National University Hospital Brain Bank (SNUH-BB)	2018-10-28	Primary age-related tauopathy	PART	PART	Korean	South Korea	Breast cancer	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 0, LB Braak: 0, Tau Braak: 2, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 1, Artherosclerosis: Mild in circle of willis.	asian	brain tissue	female	SNUH-BB : BB1817	midbrain tissue, substantia nigra	APOE : ɛ3/3	2024-06-27
KAS24091967	SNU9	77	Seoul National University Hospital Brain Bank (SNUH-BB)	2018-11-05	1. Parkinson's disease, brainstem predominant 2. Vascular dementia	PD	PD	Korean	South Korea	Dementia	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 0, LB Braak: 3, Tau Braak: 3, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 1, Artherosclerosis: Mild in circle of willis, Others: Arteriolosclerosis in Inferior parieto-occipital lobe, basal ganglia, cerebellar white matter, and pons.	asian	brain tissue	female	SNUH-BB : BB1818	midbrain tissue, substantia nigra	APOE : ɛ3/3	2024-06-27
KAS24091966	SNU8	82	Seoul National University Hospital Brain Bank (SNUH-BB)	2020-11-30	Primary age-related tauopathy	PART	PART	Korean	South Korea	Lung cancer	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 2, LB Braak: 0, Tau Braak: 3, CERAD: 1, LATE-NC (TDP-43): 0, CAA: 1, Arteriolosclerosis: 2, Artherosclerosis: 0.	asian	brain tissue	male	SNUH-BB : BB2013	midbrain tissue, substantia nigra	APOE : ɛ3/4	2024-06-27
KAS24091965	SNU5	80	Seoul National University Hospital Brain Bank (SNUH-BB)	2019-10-05	Parkison's disease, neocortical	PD	PD	Korean	South Korea	Parkinson's disease	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 2, LB Braak: 6, Tau Braak: 3, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 3, Artherosclerosis: Mild in basilar artery.	asian	brain tissue	female	SNUH-BB : BB1923	midbrain tissue, substantia nigra	APOE : ɛ3/3	2024-06-27
KAS24091964	SNU2	74	Seoul National University Hospital Brain Bank (SNUH-BB)	2019-06-11	Primary age-related tauopathy	PART	PART	Korean	South Korea	Gastric cancer	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 0, LB Braak: 0, Tau Braak: 2, CERAD: 0, LATE-NC (TDP-43): 0, CAA: 0, Arteriolosclerosis: 2, Artherosclerosis: 0, Others: Some tau-astroglipathy in the temporal lobe, amygdala and basal ganglia (privascular area of outside putamen).	asian	brain tissue	male	SNUH-BB : BB1914	midbrain tissue, substantia nigra	APOE : ɛ2/3	2024-06-27
KAS24091963	SNU1	69	Seoul National University Hospital Brain Bank (SNUH-BB)	2020-07-26	1. Parkinson's disease, neocortical 2. Alzheimer's disease neuropathologic change, intermediate (no involvement in SN)	PD	PD	Korean	South Korea	Parkinson's disease	postmortem, frozen tissue	9606	Homo sapiens	Thal phase: 4, LB Braak: 6, Tau Braak: 3, CERAD: 2, LATE-NC (TDP-43): 0, CAA: 1 (Inferior parietal lobule), Arteriolosclerosis: 1, Artherosclerosis: Mild in vertebral artery, Others: Cystic encephalomalcia, anterior orbital gyrus of the frontal lobe.	asian	brain tissue	male	SNUH-BB : BB2009	midbrain tissue, substantia nigra	APOE : ɛ3/4	2024-06-27

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