Host: Oliver Hobert
Title: Imaging the transcriptome: Spatially resolved, single-cell transcriptomics in culture and tissue
Abstract: Image-based approaches to single-cell transcriptomics—in which the expressed transcriptome of individual cells is quantified via direct fluorescent imaging of single RNA molecules—offer the exciting ability to quantify gene expression within single cells while revealing the exact spatial location of each expressed RNA molecule. I will describe multiplexed error robust single-molecule fluorescence in situ hybridization (MERFISH)—a technique capable of imaging and identifying hundreds to a thousand different RNAs simultaneously in tens of thousands of cells per day in both cell culture and tissue slices. With this technique, I have mapped the intracellular organization of the transcriptome in bacterial and human cells, performed high-throughput microscopy-based screens of pooled libraries of genetic perturbations, and discovered cell types within complex tissues. In particular, I will describe how spatially resolved, single-cell, gene-expression measurements can create cell-type- and cell-state-annotated maps of complex tissues, so called cellular atlases, and I will discuss the construction of such an atlas for a region of the mouse brain and the insight that this atlas provides in the circuits that control several instinctual social behaviors. This powerful ability to create transcriptionally defined atlases of essentially any complex tissue promises to provide a transformative new window into the molecular origins of tissue function and dysfunction in a very wide range of systems.