Single-cell and spatial alterations of neural cells and circuits in clinical and translational medicine.

The spatiotemporal heterogeneity of neurons, circuits and regulators is being uncovered at a single-cell level, from single-cell gene expression to functional regulations. The classifications, architectonics and functional communications amongst neural cells and circuits within the brain can be clearly delineated using single-cell multiomics and transomics. This Editorial highlights the spatiotemporal heterogeneity of neurons and circuits as well as regulators, initiates the translation of neuronal diversity and spatial organisation at single-cell levels into clinical considerations, and enables the discovery and development of new therapies for neurological diseases. It is predicted that single-cell and spatial multiomics will be integrated with metabolomic profiles and corresponding gene epigenetic modifications. The interactions amongst DNAs, RNAs and proteins in a cell provide details of intracellular functional regulations and new opportunities for the translation of temporospatial diversity of neural cell subtypes/states into clinical practice. The application of single-cell multiomics with four-dimensional genome to the human pathological brain will lead us to a new milestone of the diagnosis and treatment.