Journal: bioRxiv
Article Title: Context-dependent regulatory variants in Alzheimer’s disease
doi: 10.1101/2025.07.11.659973
Figure Lengend Snippet: (a) Differentiation of THP-1 monocytes into macrophages, confirmed by reduced cell cycle-related pathways and elevated immune response pathways in ATAC-seq and RNA-seq(FDR < 0.05, DESeq2, fast gene set enrichment analysis). (b) ATAC-seq of THP-1 macrophages stimulated with IFN-β, IFN-γ, or LPS+IFN-γ shows distinct regulatory responses, including promoter opening and closing (padj < 0.05, DESeq2). (c) Principal component analysis (PCA) of open chromatin profiles of THP-1 macrophages stimulated with IFN-β, IFN-γ, or LPS+IFN-γ. (d) Pathway analyses of promoters with gained accessibility under each stimulation highlight antiviral (IFN-β) and M1 polarization pathways (IFN-γ) and defense responses (LPS+IFN-γ) (FDR < 0.05, fast gene set enrichment analysis). (e) Stratified LD-score regression (S-LDSC) reveals significant enrichment of LOAD risk variants in chromatin accessible in THP-1 macrophages, comparable to primary or hESC/iPSC-derived microglia, but not in neurons or HMC3/HEK293T cells. (f) PCA of open chromatin profiles confirms that THP-1 macrophages resemble iPSC/hESC-derived microglia, whereas HMC3 is closer to immortalized cell lines. These findings validate THP-1 macrophages as a practical model for dissecting LOAD- associated immune mechanisms.
Article Snippet: HEK293T cells (AAVpro(R), Clontech, Cat. No. 632273) were cultured in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and maintained at 37°C with 5% CO2.
Techniques: RNA Sequencing, Derivative Assay
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