A Molecularly Anchored Spatial Transcriptomic Framework for Precise CA1–Subiculum Parcellation and Region-Resolved Analysis in Alzheimer’s Disease
Rattachement africain : Botswana, cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND: The precise molecular delineation of the interface between the Subiculum (Sub) and cornu ammonis 1 (CA1) is a challenge in hippocampal research, as conventional cytoarchitectural boundaries are often ambiguous and limit reproducible regional annotation. Here, we developed a molecularly anchored spatial transcriptomic framework to define CA1-Sub regional identities using high-definition spatial transcriptomics (Stereo-seq) and single-nucleus RNA sequencing (snRNA-seq) references. FINDINGS: Using a human hippocampal Stereo-seq dataset from 12 donors, we established a data-driven parcellation framework that defines reproducible molecular features distinguishing CA1 and Sub while capturing the transition between these regions. FN1 was identified as a Sub-enriched marker in a subset of EX_Sub and, together with ETV1 and additional regional markers, enabled molecular assignment of CA1 and Sub identities across datasets. The Sub association of FN1 and ETV1 was further supported by human 10X Genomics spatial transcriptomics, mouse in situ hybridization data, and a mouse spatial transcriptomic dataset. Applying this framework to Alzheimer's disease (AD) tissues revealed region-specific transcriptional alterations across CA1 and Sub, including enrichment of mitochondrial energy metabolism-related transcripts in the Sub, suggesting exploratory transcriptional associations of altered metabolic function. CONCLUSIONS: This study provides a molecularly anchored framework for human CA1-Sub parcellation that complements conventional annotation. By defining regional molecular states while preserving the biological continuum across CA1-Sub interface, this approach enables more consistent regional analysis of human hippocampus tissue across donors, datasets, and disease conditions.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A Molecularly Anchored Spatial Transcriptomic Framework for Precise CA1–Subiculum Parcellation and Region-Resolved Analysis in Alzheimer’s Disease
- Date Crossref
- 17/09/2026
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Botswana Geoscience Institute Botswana (code pays fourni par la source)Institution
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University of Chinese Academy of Sciences pays non établi dans la noticeUniversité ou école supérieure
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BGI Research pays non établi dans la noticeOrganisation à but non lucratif
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First Affiliated Hospital Zhejiang University pays non établi dans la noticeÉtablissement de santé
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College of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
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Zhejiang University School of Medicine Department of Pathology The First Affiliated Hospital pays non établi dans la noticeUniversité ou école supérieure
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Key Laboratory of Spatial Omics of Zhejiang Province pays non établi dans la noticeStructure de recherche
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Key Laboratory of Brain Cell Mapping of Zhejiang Province pays non établi dans la noticeStructure de recherche
Botswana Geoscience Institute (Botswana), University of Chinese Academy of Sciences et BGI Research, avec 5 autres affiliations. Pays d’affiliation : Botswana.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.