SUMMARY The function of human tissues is dependent upon complex interactions amongst millions of substituent cells. Tools that can systematically measure transcriptional and epigenetic states of these cells, while also recording their spatial positions, hold great promise in understanding both normal tissue function and its dysfunction in disease conditions. In this proposal, we build upon our recent invention of Slide-tags, a single-cell spatial genomics technology, to enable facile, spatial profiling of millions of cells across surface areas spanning tens of centimeters. We will extend Slide-tags to measure not only transcription, but also epigenetic states and genome variation within individual cells. Further, we will make Slide-tags profiling compatible with fixed and paraffin- embedded tissues. The innovations from this project will yield a robust, multiomic spatial platform for the routine profiling of human tissues at the scale of entire organs.