Digging into the fruit salad: elucidating the oligodendrocyte lineage using single-cell combinatorial fluidic indexing

Abstract

Within the central nervous system (CNS) oligodendrocytes ensure trophic support and insulation to neurons and they are developed in a region- and time-specific manner. In the mouse brain, oligodendrocytes were found to be specified in three developmental waves. They go from a Pdgfra+ oligodendrocyte precursor cell (OPC) through several intermediate stages to become a myelin producing mature oligodendrocyte. These distinct cell stages were previously identified using singlecell RNA sequencing (scRNA-seq). In this study, we tested a recently developed barcoding strategy that allows for enlarging the scalability of scRNA-seq, while still efficiently resolving individual transcriptomes. With single-cell combinatorial fluidic indexing (scifi-RNA-seq), we combined combinatorial and droplet-based sequencing methods and found that this assay effectively captures the marker genes of the oligodendrocyte lineage when performed on mouse and human OPCs. We see scifi-RNA-seq as a promising method to identify the complexity within mouse brain tissue. However, the barcode capacity of scifi-RNA-seq should be extended to accurately determine cell states. Future research is required to be able to distinguish rare new cell states within the oligodendrocyte cell lineage.