Imaging nuclear architecture in single cells

The smallest functional unit in our bodies, the cell, is spatially organized with various molecules, including DNA, RNA, and proteins. Studying the subcellular organization of molecules in individual cells is fundamental for understanding diverse cell types and states, from neurons to cancer cells. The cell’s nucleus—a highly organized membrane-bound organelle that contains genomic DNA in eukaryotes—is closely linked with complex gene regulation in higher organisms. Revealing its three-dimensional (3D) organization is therefore of considerable interest to a wide range of fields, including developmental biology, neuroscience, and human disease. Great advances have been made, from the groundbreaking observations of the nuclear structures in mammalian neurons under light microscopy by Santiago Ramón y Cajal in 1910 to modern genomics and imaging technologies (1, 2). However, technical limitations in the direct measurement of spatial organization of molecules in the nucleus still limit what insights can be gained into 3D nuclear architecture and gene regulation.