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

ABSTRACT: Understanding complex biological processes requires precise spatiotemporal mapping of proliferative and transcriptional dynamics. 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. It mapped regeneration dynamics, reconstructed astrocyte-to-neuron reprogramming trajectories through transient intermediates, and identified a pro‑repair niche in which newborn cells enhance neighboring developmental potency after stroke. Crucially, SPTEdU-seq simultaneously profiles newborn and resident cells within intact microenvironments, uncovering previously inaccessible interaction networks during tissue remodeling and tumor invasion. SPTEdU-seq also identified tumor‑associated splicing in mouse renal tumors and showed potential for molecular diagnosis by detecting 3p loss via CNV in human renal cell carcinoma. SPTEdU-seq establishes a powerful framework for investigating cell fate dynamics across regenerative medicine, development, and tumor biology.

ORGANISM(S): Mus musculus

PROVIDER: GSE283159 | GEO | 2026/05/14

REPOSITORIES: GEO