Figure 2. Type I IFN signal-dependent cellular senescence and inflammation in WS-iMϕs.Figure 3. Resurrection of retrotransposons in WS-iMϕs.Furthermore, silencing type I IFN signaling in WS-iMφs suppressed senescence and inflammation, enhancing proliferation (4–5-fold) (Fig. 2). Despite no external IFN trigger, WS-iMφs showed elevated type I IFN signaling, likely due to cell-intrinsic activation. We identified that retrotransposable elements (RTEs) were upregulated (Fig. 3A), forming cytoplasmic dsRNA that triggered a DHX58-mediated viral mimicry response in WS-iMφs (Fig. 2B). Knockdown of DHX58 reduced IFN signature genes (Fig. 3C). While ChIP-seq revealed decreased H3K9me3 levels at RTE loci in WS-iMφs, suggesting epigenetic derepression (Fig. 3D). The precise mechanism of RTE reactivation in WS remains unclear and requires further investigation.Direct differentiation of iPSCs into functional cells has advanced cell-based therapies, including our previous work uncovering atherosclerosis mechanisms in WS using patient-derived iPSCs 5). However, this approach is time-consuming, requires expertise, and often yields insufficient cell numbers for large-scale ― 246 ―
元のページ ../index.html#248