Fig. 4

scRNA-seq to elucidate the underlying mechanisms of hOM-MSCs in PD mice model. a UMAP of integrated transcriptomes in all groups samples of SN showing cell-type assignment, including microglia cells, oligodendrocytes, astrocytes, ECs, MPs, neuroblasts, mural cells, choroid plexus cells, T cells, B cells, ependymal cells, erythrocytes, and neutrophils. b Heatmap showing microglial M1 markers and M2 markers between nOM-MSCs treatment and hOM-MSCs treatment in the SN of PD mice. c GSEA showing the two significantly enriched pathways and the corresponding genes in the enrichment bubble map. d Gene network analysis revealed significant enrichment and interaction of PI3K-Akt/mTOR signaling pathway in microglia. e Line plots of enrichment score showed upregulation of PI3K-Akt/mTOR signaling pathway in microglia. f UMAP of integrated transcriptomes in all groups of microglia showing cell-type assignment, and ultimately segregated the microglia into seven distinct subgroups. g Dotplot showing the genes expressed in > 10% of microglia in a cluster as DEGs. h KEGG pathway dotplot showing the enrichment and up-regulation signaling pathway in microglial cells_2 and _4 in the SN of PD mice after hOM-MSCs treatment. i The cell types net graph shows the interactions between various cell populations and pinpointed the interaction between microglia and MPs as the most significant. j UMAP of integrated transcriptomes in all groups of MPs showing cell-type assignment, including macrophages, non-classic and classic mononuclear cells, cDC1, and cDC2. k Heatmap showing the cell–cell interaction analysis based on known receptor-ligand interactions between all subtypes of microglia and MPs in the SN of PD mice after hOM-MSCs treatment. l Dot graph showing the cell–cell interaction differences among the three pairs of receptor-ligands were the most significant. PI3K phosphoinositide 3-kinase, Akt protein kinase B, MPs mononuclear phagocytes, ECs endothelial cells, TGF-β transforming growth factor-β, mTOR mammalian target of rapamycin, hOM-MSCs hypoxia-olfactory mucosa mesenchymal stem cells, nOM-MSCs normoxia-olfactory mucosa mesenchymal stem cells, PD Parkinson’s disease, UMAP uniform manifold approximation and projection, SN substantia nigra, GSEA Gene Set Enrichment Analysis, KEGG Kyoto Encyclopedia of Genes and Genomes, NES normalized enrichment score, MAPK mitogen-activated protein kinase, FoxO forkhead box O, ErbB receptor tyrosine kinases, HIF-1 hypoxia inducible factor-1, JAK janus tyrosine kinase, STAT signal transducer and activator of transcription, mono mononuclear