Single-cell omics and heterogeneity of neuroglial cells

Our bodies contain a rich diversity of cell types with unique physiologic properties. Interestingly, cells within our bodies contain the same DNA content, yet they can vary dramatically with respect to their molecular, structural, and functional properties. The need to better understand cellular complexity and diversity in biologic systems has led to a technical revolution in the field through the development of sophisticated single-cell "omic" approaches. This allows the investigation of the genome, epigenome, transcriptome, and proteome of individual cells derived from complex samples or tissues, such as nervous system tissue. These methods are allowing scientists to detect distinct cell populations and cellular states in different species (including rodent and human) and molecular transitions of cell populations across the lifespan. Recent studies have revealed that astrocytes, oligodendrocytes, and microglia exhibit greater molecular and functional heterogeneity than originally thought and innovative single-cell technologies have allowed a more comprehensive and less biased view of this cellular diversity. The chapter begins by providing a primer of single-cell transcriptomic and spatial transcriptomic approaches that have been particularly influential in uncovering single-cell diversity of neuroglial cells in the brain. It then takes a closer look at how these technologies have been pivotal in defining neuroglial cell subtypes and for determining their spatial relationships within the CNS. Then, it concludes with discussion of how the recent technical advances and discoveries have provoked new questions about the origin, organization, and functional purpose of diverse neuroglial cell subtypes.