A new spatial transcriptomic approach captures the regulation of splicing and polyadenylation sites during pubescent brain development at near-single-cell resolution. An international collaboration, led by researchers from Weill Cornell University (NY, USA), has developed a new spatial approach to investigate critical RNA processing steps in the brain, both before and after puberty. This approach, combining long- and short-read sequencing with an innovative spatial technology, overcomes the challenges of studying these processes within their biological context, offering greater insight into brain development. Puberty represents a period of developmental change, which can affect brain plasticity characterized by changes in RNA splicing and polyadenylation. However, investigating which areas of the brain are most strongly altered by these modifications has been a challenge, due to a reliance on low-resolution technologies with insufficient transcript capture efficiency. A micron-resolution map for navigating tissue fiber networks A new method has revolutionized our ability to map tissue fiber orientation and organization across tissues, diseases and sample preparations. To overcome the limitations of traditional methods, the researchers have combined long- and short-read sequencing with Slide-SeqV2 (Seeker™ technology) to observe the developmental regulation of splicing and polyadenylation that occurs in specific cortical layers and cell types during puberty. Their running of both long- and short-read sequencing in tandem meant that they were able to describe transcript information spanning multiple exons while also conducting gene-expression based analyses, offering the greatest transcriptomic insight into the tissue. Their cell type-specific spatial transcriptomic approach is called spatial isoform sequencing (Spl-ISO-Seq); it spatially barcodes RNA…
