Spatial transcriptomic imaging of an intact organism using volumetric DNA microscopy.

ABSTRACT: Lymphatic, nervous and tumor tissues exhibit complex physiology arising from three-dimensional interactions within genetically unique microenvironments. Here we develop a technology capable of volumetrically imaging transcriptomes, genotypes and morphologies in a single measurement, without relying on prior knowledge of spatial organization or genetic sequences. Our method extends DNA microscopy into three dimensions at scales involving 10⁷ molecules by forming a distributed intermolecular network of proximal unique DNA barcodes tagging complementary DNA molecules inside the specimen. After sequencing the DNA-encoded network, an image of molecular positions is inferred using geodesic spectral embeddings, a dimensionality reduction approach that we show to be especially suitable

SUBMITTER: Qian N 

PROVIDER: S-EPMC12339006 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature