( A) t-SNE showing isocortical clusters (categorical color scheme). Molecular similarity colors based on median coordinates of spots per cluster in the 3D t-SNE shown in (C) to (E), (G), and (I). ( J) Virtual sectioning of the molecular atlas (black line shows example of horizontal or a sagittal plane). ( I) Example coronal sections from the molecular atlas (left side, ABA reference atlas right side, molecular clusters color-coded on the basis of molecular similarity). Right side: The same clusters shown in the molecular atlas (black lines, molecular cluster borders). Left side: Position and molecular identity of spots for selected clusters (black lines, ABA region borders). ( H) Example coronal sections from the molecular atlas. Outer layer colored according to ABA subregions. Inner layer is color-coded using molecular similarity. Molecular clusters annotated with a numerical identifier and a name according to correspondence to ABA subregion. ( G) Hierarchical clustering of the 181 molecular clusters (fan plot). ( F) 2D t-SNE showing spots according to ABA neuroanatomical regions. ( E) 2D t-SNE showing spots according to molecular similarity coloring. ( D) Mapping of all spots in 3D colored by molecular similarity. ( C) 3D t-SNE to visualize molecular similarity of clusters. ( B) 2D t-SNE with categorical color scheme to visualize spots in 181 molecular cluster (27 unique colors). IC scores above the 95th percentile in absolute value are shown in 3D. Right side: Corresponding ABA reference section. ( A) Examples of ICs (biological versus technical). Color scheme in (C) to (E), based on ABA reference color scheme. Composite 3D image showing expression of all three genes including region definitions. Left hemisphere shows striatum (light blue) and thalamus (light red) in ABA. In 3D, right hemisphere shows spots with gene expression level above the 95th percentile. Left side, expression in the molecular atlas right side, ISH signal from ABA. ( F) Expression of three candidate genes with spatially discrete signals: in isocortex (Rasgrf2, green), striatum (Gpr88, blue), and thalamus (Rora, red). ( E) Distribution of all spots according to main ABA region definitions. ( D) 3D mapping of all spots color-coded according to main region identity. ( C) Transformation (light blue lines) of section shown in (B) to generate a common reference framework containing ST spot position and ABA neuroanatomical definitions. ( B) Example of image processing showing the section outline in 3D (top left), the H&E-stained coronal section (top right), alignment with the ST array (bottom left), and alignment with the ABA mouse brain reference atlas (bottom right). Adjacent sections shown with light and dark red color. ( A) Distribution of coronal sections used to generate the molecular atlas. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). In summary, we have established a molecular atlas to formally define the spatial organization of brain regions, including the molecular code for mapping and targeting of discrete neuroanatomical domains.Ĭopyright © 2020 The Authors, some rights reserved exclusive licensee American Association for the Advancement of Science. The molecular atlas further supports the characterization of the spatial identity of neurons from their single-cell RNA profile, and provides a resource for annotating the brain using a minimal gene set-a brain palette. The unsupervised (non-expert, data-driven) classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and new subdivisions of striatum. We found that the molecular information was sufficient to deduce the complex and detailed neuroanatomical organization of the brain. ![]() We aimed to generate a systematic classification of the adult mouse brain based purely on the unbiased identification of spatially defining features by employing whole-brain spatial transcriptomics. Brain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |