Patch-seq: Multimodal Profiling of Single-Cell Morphology, Electrophysiology, and Gene Expression

Cells exhibit diverse morphologic phenotypes, biophysical and functional properties, and gene expression patterns. Understanding how these features are interrelated at the level of single cells has been challenging due to the lack of techniques for multimodal profiling of individual cells. We recently developed Patch-seq, a technique that combines whole-cell patch clamp recording, immunohistochemistry, and single-cell RNA-sequencing (scRNA-seq) to comprehensively profile single cells. Here we present a detailed step-by-step protocol for obtaining high-quality morphological, electrophysiological, and transcriptomic data from single cells. Patch-seq enables researchers to explore the rich, multidimensional phenotypic variability among cells and to directly correlate gene expression with phenotype at the level of single cells.