Cell Type–Specific Nuclei Markers: The Need for Human Brain Research to Go Nuclear.

This article focuses on identifying and consolidating robust cell type–specific nuclear markers for the major human brain cell types—neurons, microglia, astrocytes, oligodendrocytes, endothelial cells, and pericytes—to improve the precision of neuroscientific research. It highlights the limitations of traditional whole-cell markers, which target cytoplasmic or membrane proteins, and emphasizes the advantages of nuclear markers for applications such as immunohistochemistry, fluorescence-activated nuclei sorting (FANS), and single-nucleus RNA sequencing (snRNA-seq), especially in archived human brain tissue. Key nuclear markers discussed include NeuN for neurons, PU.1 for microglia, SOX9 for astrocytes, OLIG2 for oligodendrocytes, ERG for endothelial cells, and ZIC1 and KLF-3 as prospective markers for pericytes. The review also addresses the specificity and caveats of these markers across different brain regions and disease states, underscoring their potential to enhance cell type–specific transcriptomic analyses and downstream applications in neurological disease research.