GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE324nnn/GSE324753/primary200OKOtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324753GEOGSEfalseHighly sensitive, sub-micron spatial host-microbiome transcriptomics in FFPE tissues via iterative hydrogel expansionSpatial transcriptomics (ST) of clinical formalin-fixed paraffin-embedded (FFPE) tissues is fundamentally limited by a trade-off between spatial resolution and transcriptomic sensitivity due to severe molecular crowding and RNA degradation. Here, Ex-spRandom is presented, a highly sensitive platform that integrates random-primed in situ cDNA synthesis with an interpenetrating polymer network (IPN)-based tissue expansion protocol. This physicochemical synergy physically decrowds the dense FFPE matrix, directly converting fragmented host and microbial RNAs into stably anchored cDNA. Consequently, Ex-spRandom translates macro-scale arrays into a sub-micron effective resolution of ~0.9 µm while achieving an unprecedented transcriptomic sensitivity exceeding 40,000 unique genes per sample. This platform successfully rescues non-coding regulatory transcripts and unmasks continuous neurodevelopmental trajectories in the dense embryonic eye. Furthermore, it enables the simultaneous, high-fidelity spatial mapping of host epithelial architectures alongside localized resident microbiomes in the colon. By breaking the resolution-sensitivity barrier without aggressive proteolysis, Ex-spRandom establishes a highly scalable framework for deciphering complex structural and functional microenvironments across vast archival clinical cohorts.2026/08/26GSE324753GSM9584942GSM9584943GSM9584940GSM9584941GSM9584946GSM9584944GSM9584945GSM9584939GSM958493824247324753Mus musculus[42605963]