Comprehensive mapping of tissue cell architecture via integrated single cell and spatial transcriptomics

TLDR

The spatial organization of cell types in tissues shapes cellular interactions and function, yet high‑throughput spatial mapping of complex tissues remains challenging. The study aims to provide a comprehensive, high‑throughput method for mapping cell types in situ by integrating single‑cell and spatial transcriptomics. The authors develop a Bayesian model, cell2location, that integrates single‑cell and spatial transcriptomics and apply it to a paired single‑nucleus and spatial RNA‑seq dataset from mouse brain to automatically map dozens of cell types and tissue regions. Cell2location outperforms existing tools in accuracy and comprehensiveness, identifies novel regional astrocyte subtypes in mouse brain, resolves interlaced immune cell states and co‑located groups in human lymph node, maps a rare pre‑germinal centre B‑cell population with predicted interferon‑related interactions, and demonstrates its utility as a versatile first‑line analysis tool for high‑throughput tissue architecture mapping.

Abstract

Abstract The spatial organization of cell types in tissues fundamentally shapes cellular interactions and function, but the high-throughput spatial mapping of complex tissues remains a challenge. We present сell2location, a principled and versatile Bayesian model that integrates single-cell and spatial transcriptomics to map cell types in situ in a comprehensive manner. We show that сell2location outperforms existing tools in accuracy and comprehensiveness and we demonstrate its utility by mapping two complex tissues. In the mouse brain, we use a new paired single nucleus and spatial RNA-sequencing dataset to map dozens of cell types and identify tissue regions in an automated manner. We discover novel regional astrocyte subtypes including fine subpopulations in the thalamus and hypothalamus. In the human lymph node, we resolve spatially interlaced immune cell states and identify co-located groups of cells underlying tissue organisation. We spatially map a rare pre-germinal centre B-cell population and predict putative cellular interactions relevant to the interferon response. Collectively our results demonstrate how сell2location can serve as a versatile first-line analysis tool to map tissue architectures in a high-throughput manner.