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Integration of Imaging-based and Sequencing-based Spatial Omics Mapping on the Same Tissue Section via DBiTplus

ABSTRACT: DBiTplus utilizes in situ reverse transcription, in-tissue delivery of DNA oligos for spatial barcoding, and RNaseH-mediated selective cDNA retrieval, preserving tissue architecture to enable highly multiplexed protein imaging and spatial transcriptomics on the same slide. Computational pipelines seamlessly integrates these modalities, allowing imaging-guided deconvolution to generate genome-scale, single-cell-resolved spatial transcriptome atlases. DBiTplus was demonstrated across diverse samples including mouse embryos, normal human lymph nodes, and formalin-fixed paraffin-embedded (FFPE) human lymphoma tissues, highlighting its compatibility with challenging clinical specimens. Applying DBiTplus to human lymphoma samples reveals key mechanisms driving lymphomagenesis, progression, and notably, the progression of indolent marginal zone lymphoma (MZL) or the transformation from chronic lymphocytic leukemia (CLL) to diffuse large B-cell lymphoma (DLBCL), including uniquely, the spatially resolved involvement of microRNAs in modulating the transformation dynamics. Thus, DBiTplus is a unified workflow including integrative experimental procedure and computational innovation for spatially resolved single-cell atlasing and exploration of biological pathways cell-by-cell at genome-scale.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE308167 | GEO | 2025/10/04

REPOSITORIES: GEO

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