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

Abstract

Identifying and interrogating cell type-specific populations within the heterogeneous milieu of the human brain is paramount to resolving the processes of normal brain homeostasis and the pathogenesis of neurological disorders. While brain cell type-specific markers are well established, most are localized on cellular membranes or within the cytoplasm, with limited literature describing those found in the nucleus. Due to the complex cytoarchitecture of the human brain, immunohistochemical studies require well-defined cell-specific nuclear markers for more precise and efficient quantification of the cellular populations. Furthermore, efficient nuclear markers are required for cell type-specific purification and transcriptomic interrogation of archived human brain tissue through nuclei isolation-based RNA sequencing. To sate the growing demand for robust cell type-specific nuclear markers, we thought it prudent to comprehensively review the current literature to identify and consolidate a novel series of robust cell type-specific nuclear markers that can assist researchers across a range of neuroscientific disciplines. The following review article collates and discusses several key and prospective cell type-specific nuclei markers for each of the major human brain cell types; it then concludes by discussing the potential applications of cell type-specific nuclear workflows and the power of nuclear-based neuroscientific research.

Keywords: astrocytes; brain cell nuclei; cell type-specific; endothelial cells; flow cytometry; fluorescence-activated cell sorting; immunohistochemistry; microglia; neuron; nuclear markers; oligodendrocytes; pericytes; single-nucleus RNA-seq.