Multi-omics reveals heterogeneity and functional populations of oligodendrocyte progenitor cells induced by human neural stem cells

Heterogeneity is widely recognised across different cell types. Human oligodendrocyte progenitor cells (hOPCs), essential for myelination, exhibit considerable heterogeneity, which has not been fully characterised. In the current study, by examining the transcriptome of hOPCs at the single-cell level, three distinct subclusters were identified: PRE-OPCs, OPCs, and PRE-OLs. Single-cell RNA-sequencing and RNA-Scope detected high platelet-derived growth factor receptor alpha (PDGFRA) expression. PDGFR-α⁺ hOPCs exhibited greater myelination, migration, and proliferation capabilities compared to both unsorted hOPCs and PDGFR-α^- hOPCs. These enhanced functions may be associated with the activation of the PI3K-AKT-mTOR and TGF-β signalling pathways, which support oligodendrocyte differentiation. hOPCs were induced by hNSCs, their characteristics were identified. RNA-Scope and single-cell RNA Seq sequencing showed PDGFRA were highly expressed at mRNA and protein level. hOPCs were sorted by MACS using PDGFR-α beads. The myelination, migration, and proliferation abilities of PDGFR-α⁺ hOPCs were higher than that of un-sorting hOPCs and PDGFR-α^- hOPCs, possibly being associated with the activation of PI3K-AKT-mTOR and TGF-β signalling pathways, which support oligodendrocyte differentiation (Partly created with Scientific Image and Illustration Software BioRender).