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High-resolution spatial transcriptomics of DARLIN mouse [CRISPR array amplicon]

ABSTRACT: Spatially-resolved single-cell lineage tracing is a powerful approach for studying cell lineages and fate decisions in situ. However, existing studies are limited to specific cell types such as lymphocytes and cancer cells. We recently developed DARLIN, a lineage tracing mouse model that has massive lineage barcodes and efficient barcode recovery. Here, we present Spatio-DARLIN, a generic spatial lineage tracing tool that integrates sequencing-based spatial transcriptomics with DALRIN mouse. Applying it to the small intestine, we observed a high-quality transcriptome with nearly single-cell resolution and recovered ~25% cells with reliable lineage barcodes, resulting in ~7000 clones with >1 cell per tissue section. These clones showed highly reproducible spatial localization across adjacent tissue sections, confirming their accuracy. With this high-throughput approach, we observed that intestinal epithelial clones were localized along the crypt-villus axis and underwent vertical expansion over a longer tracing period. Since DARLIN is publicly available and labels cells across most tissues, Spatio-DARLIN offers an accessible and efficient approach for spatial lineage tracing across various mouse tissues with high resolution.

ORGANISM(S): Mus musculus

PROVIDER: GSE296897 | GEO | 2026/04/12

REPOSITORIES: GEO

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