Journal: bioRxiv

Article Title: Context-dependent regulatory variants in Alzheimer’s disease

doi: 10.1101/2025.07.11.659973

Figure Lengend Snippet: (a) Differential expression analyses confirm significant up- or downregulated genes under various stimulation conditions (FDR < 0.05, DESeq2). (b) Gene set enrichment analyses of resting and stimulated THP-1 macrophages reveal immune-related shifts (IFN-β, IFN-γ, LPS+IFN-γ) that mirror ATAC-seq changes in . (FDR < 0.05, fast gene set enrichment analysis). (c) PCA of RNA-seq data shows distinct transcriptomic clusters for each state, reflecting diverse immune states. (d) Microglial and macrophage markers were expressed in all conditions. (e) Differential expression of microglial-state marker genes (Sun et al. ) in stimulated THP-1 macrophages versus non-marker genes (two-sided Mann-Whitney U, Benjamini- Hochberg correction). Significance codes, Benjamini-Hochberg FDR: **** < 1 × 10⁻⁴; *** < 1 × 10⁻³; ** < 1 × 10⁻²; * < 0.05; NS, not significant. (f) Transcriptomic concordance between LPS + IFN-γ-stimulated THP-1 macrophages and amyloid-fibril-treated iPSC-microglia. Pearson’s r is calculated on the expression levels of genes that are differentially expressed in the amyloid-fibril model (Sun et al. ).

Article Snippet: HMC3 microglia-like cells (ATCC CRL-3304) were cultured in Microglial Cell Medium Kit (Accegen, ABI-TM009) and maintained at 37°C with 5% CO2.

Techniques: Quantitative Proteomics, RNA Sequencing, Marker, MANN-WHITNEY, Expressing

Journal: bioRxiv

Article Title: Context-dependent regulatory variants in Alzheimer’s disease

doi: 10.1101/2025.07.11.659973

Figure Lengend Snippet: (a) Hi-C in THP-1 macrophages (<5-kb resolution) places the enhancer (black bar) in the same contact domain as the SEC63 promoter and shows a looping interaction with the OSTM1 promoter and a CTCF anchor in the intronic regions of AFG1L (b) Three-dimensional chromatin model of the SEC63-OSTM1 enhancer and nearby genes. (c) SEC63 , the enhancer, and OSTM1 knockdown in hyperinflammatory (LPS + IFN-γ- treated) THP-1 macrophages. (d) CRISPRi knockdown of the SEC63 and OSTM1 promoters perturbs distinct transcriptional pathways in resting and hyperinflammatory (LPS + IFN-γ-treated) THP-1 macrophages (fgsea, FDR<0.05). (e) Expression of the microglial-state marker genes defined by Sun et al. after CRISPRi. Silencing SEC63 shifts multiple microglial programs, and these shifts are amplified under LPS + IFN-γ-highlighting a central role for SEC63 in state transitions and immune responses.

Article Snippet: HMC3 microglia-like cells (ATCC CRL-3304) were cultured in Microglial Cell Medium Kit (Accegen, ABI-TM009) and maintained at 37°C with 5% CO2.

Techniques: Hi-C, Knockdown, Expressing, Marker, Amplification