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An integrated single-nucleus and spatial transcriptomics atlas reveals the molecular landscape of the human hippocampus.
Nelson, Erik D; Tippani, Madhavi; Ramnauth, Anthony D; Divecha, Heena R; Miller, Ryan A; Eagles, Nicholas J; Pattie, Elizabeth A; Kwon, Sang Ho; Bach, Svitlana V; Kaipa, Uma M; Yao, Jianing; Kleinman, Joel E; Collado-Torres, Leonardo; Han, Shizhong; Maynard, Kristen R; Hyde, Thomas M; Martinowich, Keri; Page, Stephanie C; Hicks, Stephanie C.
Afiliación
  • Nelson ED; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Tippani M; Cellular and Molecular Medicine Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Ramnauth AD; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Divecha HR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Miller RA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Eagles NJ; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Pattie EA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Kwon SH; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Bach SV; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Kaipa UM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Yao J; Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Kleinman JE; Biochemistry, Cellular, and Molecular Biology Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Collado-Torres L; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Han S; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Maynard KR; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Hyde TM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Martinowich K; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
  • Page SC; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Hicks SC; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
bioRxiv ; 2024 Apr 28.
Article en En | MEDLINE | ID: mdl-38712198
ABSTRACT
The hippocampus contains many unique cell types, which serve the structure's specialized functions, including learning, memory and cognition. These cells have distinct spatial topography, morphology, physiology, and connectivity, highlighting the need for transcriptome-wide profiling strategies that retain cytoarchitectural organization. Here, we generated spatially-resolved transcriptomics (SRT) and single-nucleus RNA-sequencing (snRNA-seq) data from adjacent tissue sections of the anterior human hippocampus across ten adult neurotypical donors. We defined molecular profiles for hippocampal cell types and spatial domains. Using non-negative matrix factorization and transfer learning, we integrated these data to define gene expression patterns within the snRNA-seq data and infer the expression of these patterns in the SRT data. With this approach, we leveraged existing rodent datasets that feature information on circuit connectivity and neural activity induction to make predictions about axonal projection targets and likelihood of ensemble recruitment in spatially-defined cellular populations of the human hippocampus. Finally, we integrated genome-wide association studies with transcriptomic data to identify enrichment of genetic components for neurodevelopmental, neuropsychiatric, and neurodegenerative disorders across cell types, spatial domains, and gene expression patterns of the human hippocampus. To make this comprehensive molecular atlas accessible to the scientific community, both raw and processed data are freely available, including through interactive web applications.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos