Molecular Medicine Israel

Cell-type modeling in spatial transcriptomics data elucidates spatially variable colocalization and communication between cell-types in mouse brain

Highlights

  • A neural network, STANN, models cell types in single-cell spatial transcriptomics data
  • Subsequent analyses reveal mouse brain architecture beyond conventional layers
  • Cellular colocalization and communications could show high variations within a layer
  • Spatially localized subpopulations of cell types differ in receptor-ligand usage

Summary

Single-cell spatial transcriptomics (sc-ST) holds the promise to elucidate architectural aspects of complex tissues. Such analyses require modeling cell types in sc-ST datasets through their integration with single-cell RNA-seq datasets. However, this integration, is nontrivial since the two technologies differ widely in the number of profiled genes, and the datasets often do not share many marker genes for given cell types. We developed a neural network model, spatial transcriptomics cell-types assignment using neural networks (STANN), to overcome these challenges. Analysis of STANN’s predicted cell types in mouse olfactory bulb (MOB) sc-ST data delineated MOB architecture beyond its morphological layer-based conventional description. We find that cell-type proportions remain consistent within individual morphological layers but vary significantly between layers. Notably, even within a layer, cellular colocalization patterns and intercellular communication mechanisms show high spatial variations. These observations imply a refinement of major cell types into subtypes characterized by spatially localized gene regulatory networks and receptor-ligand usage.

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