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Spatial transcriptomic analysis of human dorsoal root ganglia neurons [Xenium]

ABSTRACT: Xenium platform was used for the spatial transcriptomic analysis of human DRG neurons, 100 marker genes were selected as the customized probe panel and hybridized to fresh frozen hDRG sections. Manual segmentation of each neuron soma was performed, based on expressions of pan-neuronal marker gene PGP9.5, satellite glia cell marker FAB7B, and the corresponding H.E. staining. In total, 1340 neurons were identified (excluding 75 region-of-interest with poor or unclear neuronal soma morphology in H & E staining) and clustered into 16 groups. The 16 clusters were assigned as different cell types based on marker genes expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE273557 | GEO | 2024/08/14

REPOSITORIES: GEO

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Project description:The hypothalamus (HYP) underlies basal endocrine, physiological, and behavioral drives which inherently differ across species and sexes—ranging from growth and puberty to appetite and metabolism to social behavior. Especially in the rodent brain, these sex-differentiated functions correspond to differences in the volume, cell types, and gene expression of distinct HYP subareas. Recent studies have elucidated the transcriptional profile of single cells in the rodent ventromedial hypothalamus (VMH) and arcuate (ARC), which influence appetitive/social behaviors and growth/metabolism, respectively. However, there is a paucity of studies examining the molecular architecture of the adult human HYP, and transcriptional sex differences in the human VMH and ARC have not been characterized in single-cell or spatial contexts. Using 10x Genomics Visium and Xenium platforms, we generated a multimodal, spatially-resolved molecular atlas of human postmortem VMH and ARC from male and female adult donors. Sex-differential gene expression analysis within these regions revealed correlated autosomal expression differences, with stronger overall sex effects in the ARC. We then leveraged the single-cell-resolution of Xenium to localize sex-differential expression to cell types, finding most occur in ESR1- and KISS1-expressing neurons of the ARC. Finally, we investigated VMH and ARC gene expression in relation to genes associated with neuropsychiatric diseases, identifying a striking enrichment of genes upregulated in the male VMH for known and candidate risk genes for autism spectrum disorders. This work provides a multisample view of the human VMH and ARC in young/middle adulthood across both sexes, including data at both transcriptome-wide and single-cell resolutions, the first single-cell transcriptional atlas of molecular sex differences in the adult human VMH and ARC, and highlights potential sex-differentiated roles for VMH and ARC in neurobehavioral disorders.

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Spatial transcriptomic analysis of human dorsoal root ganglia neurons [Xenium]

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