SPTEdU-seq: Parallel optics-free newborn cell tracking and spatial total transcriptomics decipher spatiotemporal dynamics across tissues and species

Current spatial transcriptomics methods are tailored to capture protein-coding transcripts and static snapshots, obscuring non-coding RNAs and dynamic cellular events. We developed SPTEdU-seq, integrating spatial full-length total transcriptomics with optics-free 5-ethynyl-2’-deoxyuridine (EdU) tracking to concurrently profile global gene expression and proliferation dynamics at cellular resolution.

SPTEdU-seq demonstrates ultrahigh sensitivity in detecting coding/non-coding transcripts and splicing isoforms, and bypasses imaging through its single-molecule probe design. Applied to the developing and adult mouse brains, it revealed spatial lncRNA patterns, reconstructed cortical trajectories through enhanced RNA velocity and enabled spatiotemporal lineage tracing of embryonic neurodevelopment. To demonstrate its applicability across pathological contexts, SPTEdU-seq was applied to murine ischemic stroke as well as mouse and human renal tumors.