Journal: Frontiers in Dementia
Article Title: Neurogenesis drives hippocampal formation-wide spatial transcription alterations in health and Alzheimer's disease
doi: 10.3389/frdem.2025.1546433
Figure Lengend Snippet: Transcription profile of the hippocampal formation. (a) Mouse genotypes. C–NB: Nestin-CreER T2 ;Bax fl/fl injected with corn oil (vehicle). T–NB: Nestin-CreER T2 ;Bax fl/fl injected with tamoxifen. C–NBF: Nestin-CreER T2 ;Bax fl/fl ;5XFAD injected with corn oil. T–NBF: Nestin-CreER T2 ;Bax fl/fl ;5XFAD injected with tamoxifen. (b) Immunofluorescence staining of coronal mouse dentate gyrus (DG) for each group. Red: NeuN; white: DCX. Scale bar indicates 100 μm. (c) Experiment design. 10 μm coronal sections were isolated from each animal and processed for Cartana in situ sequencing, cell segmentation, and analysis. (d) Representative spatial scatter plot of spots for a sample of genes including Prox1, Neurod6, Rbfox3 (green, neuron-related), Mbp, Plp1 (cyan, oligodendrocyte-related), Acqp4, Aldoc (orange, astrocyte-related), and Laptm5, Itgam (blue, microglia-related). Atlas schematic of approximate coronal slice location used for analysis. The hippocampal formation including entorhinal cortex (EC) is highlighted in red. (f) Cells per mm 2 for each region of the hippocampal formation. The color indicates the average across all samples for each region. (g) Histogram of the number of unique genes expressed per cell. (h) Bar plot of the 10 most highly expressed genes across all cells. (i) Heatmap of the union top ten (32 unique) most highly expressed genes by region. Color indicates the percent expression (column) z -score for each gene in each region. (j, k) UMAP embedding of binned gene spot counts. Each point represents a 50 μm2 area of tissue. Color indicates either group (j) or region (k) . (l) UMAP representation of a selection of genes shown in (i) . Color indicates normalized ln(1+ x ) (i.e., log1p) gene expression. (m) Sankey diagram depicting the quantity of cell types in each region for each group. (n) Dot plot of the number of genes restored in the different cell types in each region of the hippocampal formation, in T–NBF, resembling their expression in C–NB, rather than C–NBF. The size and color of each dot indicates the number of restored genes in T–NBF for each cell type and region.
Article Snippet: We used in situ sequencing (spatial transcriptomics) to investigate the transcription profile of neurons and glia in the hippocampal circuitry of a mouse model of AD with varying levels of neurogenesis.
Techniques: Injection, Immunofluorescence, Staining, Isolation, In Situ, Sequencing, Expressing, Selection, Gene Expression
