Figure 4.

Trajectory reconstruction reveals astrocyte differential activation, loss of myelinating oligodendrocytes, and differential activation in idiopathic Parkinson’s disease (IPD). (A) Astroglial subpopulations are named based on characteristic marker genes. (B) VAV3, LRRC4C, CD44, and S100A6 expression across the ∼4700 astrocytes. (C) Inferred cell trajectory and pseudotime for the major astrocyte subpopulations, VAV3^high, LRRC4C^high and CD44^high cells. (D) Idiopathic Parkinson’s disease and control differential cell-density distribution over pseudotime and the expression of the 94 genes highly associated with the astrogliosis trajectory in the ∼4700 astrocytes organized by pseudotime. (E) GO molecular function pathway enrichment of the upregulated genes in the CD44^high activated branch. (F) The 34 intersected genes between the upregulated genes in idiopathic Parkinson’s disease and across the astrocyte activation trajectory. (G) Oligodendrocyte subpopulations are named based on representative marker genes. (H) Expression of OPALIN, RBFOX1, FRY and S100B in the ∼21 000 oligodendrocytes. (I) Inferred cell trajectory and pseudotime ordering of the major oligodendrocytes subpopulations, OPALIN^high, ATP6V0D2^high, and S100B^high cells. (J) Idiopathic Parkinson’s disease and control differential cell density over pseudotime. Expression levels of 790 highly variable genes across the oligodendrocyte trajectory. Expression is presented for ∼21 000 oligodendrocytes organized by their pseudotime. (K and L) The intersection of idiopathic Parkinson’s disease differentially expressed and trajectory-associated genes. Also, the GO molecular enrichment of the intersected genes is presented. (K) Two hundred and sixteen idiopathic Parkinson’s disease downregulated genes across the trajectory are associated with pathways important for neuron projection and synaptic transmission. (L) Three hundred and thirty genes are idiopathic Parkinson’s disease upregulated along the oligodendrocyte trajectory. These genes are mainly associated with the unfolded protein response.