MERFISH Enables Mapping of Cellular Diversity with Spatial Context at Subcellular Resolution

The brain, a lung, a tumor: each contains a complex array of cell types arranged in an intricate spatial pattern that is critical to their role within the tissue. While work is underway to create an atlas of cellular diversity across tissues, traditional methods either have sufficiently high multiplexing capacity but lack spatial context, or they provide spatial information but lack the multiplexing capacity to identify subtle variations in cell type or state. This limitation precludes a comprehensive view across a whole tissue, including rare cells, as they exist within a tissue of interest. Since understanding how the molecular and cellular organization of a biological tissue contributes to its functionality is fundamental to developing treatments that target the cell biology underlying diseased states, improved tools that map biological systems with both high spatial resolution and high multiplexing capacity promise to deliver new, clinically relevant insights into the functional composition of biological systems. The recently developed multiplexed error-robust fluorescence in situ hybridization (MERFISH) method provides information about gene expression at subcellular resolution and reveals cell type, state, and cell-cell interaction by quantifying the expression and exact location of hundreds to thousands of transcripts within intact tissues. MERFISH represents a major advancement toward directly interrogating rich cellular heterogeneity and is being applied to gain insight into the biological complexity within and around us.