In Situ Sequencing of Tissues - a New Technology to Merge Imaging with Genomics

Next-generation sequencing of RNA from tissues and single cells has transformed biology by starting to provide the molecular basis behind the function of cells and tissues. However, so far all the RNA sequencing methods involved grinding up or dissociating the cells before sequencing, thereby destroying all spatial information about the cells in relation to the tissue. On the other hand, optical methods maintain the spatial location of RNA molecules, but are limited in the number of molecules that can be studied simultaneously. New technologies to map the locations of RNAs throughout the morphologies of cells in intact tissues are beginning to emerge, but to date have been restricted to pre-defined list of targeted genes. I will present the ability to perform in situ sequencing in an untargeted way, therefore allowing to survey the transcriptome and to discover sequence variants such as alternative splicing. This technology, expansion sequencing, enables comprehensive spatial mapping of gene expression with subcellular resolution.