Full-length spatial transcriptome strategy based on robust and low-cost target tissue capture

Smart-seq2, a widely used method for constructing full-length mRNA transcriptome libraries, can be combined with target tissue capture techniques such as Laser Capture Microdissection (LCM) to achieve robust spatial transcriptomic profiling. However, both Smart-seq2 and LCM are limited by high costs and complex operation, hindering their broader adoption. Here, we report a full-length spatial transcriptome strategy based on a robust and cost-effective tissue capture technique, termed MSN-seq. MSN-seq integrates microneedle-based sampling with a modified Smart-seq2 protocol. This method captures multi-cellular tissue spots and not only optimises Smart-seq2 for enhanced performance but also leverages reusable steel needles to further reduce costs and improve transcriptomic capture efficiency. In addition to simplifying experimental procedures, MSN-seq increases accessibility by enabling spatial transcriptomic analysis without requiring specialised skills or expensive instrumentation. We applied MSN-seq to brain and retinal tissues from models of Parkinson's disease and retinal degeneration, demonstrating its effectiveness in capturing spatial transcriptomic data. Furthermore, application of MSN-seq to frozen sections from U251 glioblastoma model mice revealed early invasive mechanisms and spatially restricted enrichment of immune cell subsets. Overall, MSN-seq provides a low-cost, easy-to-use, and highly efficient strategy for acquiring spatial transcriptome data.