Fig. 3

ATAC-seq combined with ISO-seq to elucidate the underlying mechanisms of hOM-MSCs in PD cell model. a Enrichment heatmap of ATAC-seq differential peak before and after hypoxic pretreatment of OM-MSCs. Each row is a differential peak, and each column is a sample. b Differential gene enrichment heatmap before and after hypoxic pretreatment of OM-MSCs. The horizontal coordinate represents the sample name and sample clustering results, and the vertical coordinate represents the differential genes and gene clustering results. c The intersection differential genes of ATAC-seq and ISO-seq are jointly displayed by clustering heatmap to visually display the dual changes of chromatin accessibility and expression level of genes. d Annotation results of DEGs were classified according to KEGG pathway types before and after hypoxic pretreatment of OM-MSCs. e The network relationships of the top 20 signaling pathways enriched by KEGG and their corresponding genes were mapped. f IGV visualized LTBP1 and TGF-β1 in the results of combined analysis of ATAC-seq and ISO-seq before and after hypoxic pretreatment of OM-MSCs. g RT-qPCR and Western blotting measuring the expression of LTBP1 and TGF-β1 mRNA and protein in OM-MSCs before and after hypoxia pretreatment. h ELISA showing a histogram of the concentration of TGF-β1 in OM-MSCs cells and supernatant both before and after hypoxia pretreatment. i Hierarchical cluster analysis was performed on the DEGs screened from microglia of the PD cell model, and the genes with the same or similar expression patterns were drawn into clustering heat maps. j Annotation results of DEGs were classified according to KEGG pathway types in microglia of the PD cell model after hOM-MSCs intervention. k The network relationships of the top 4 signaling pathways enriched by KEGG and their corresponding genes were mapped in the microglia of the PD cell model after hOM-MSCs intervention. ^**P < 0.01, ^****P < 0.0001. OM-MSCs olfactory mucosa mesenchymal stem cells, hOM-MSCs hypoxia-olfactory mucosa mesenchymal stem cells, KEGG Kyoto Encyclopedia of Genes and Genomes, TGF-β1 transforming growth factor-β1, LTBP1 latent transforming growth factor beta binding protein 1, DEGs differentially expressed genes, IGV integrative genomics viewer, ATAC-seq assay for transposase-accessible chromatin with high-throughput sequencing, ISO-seq isoform-sequencing, PD Parkinson’s disease, FC fold change, NF-κB nuclear factor kappa-B, PPAR peroxisome proliferator-activated receptor, FoxO forkhead box O