来自炎症性肠病患者的肠干细胞保留了炎症的表观遗传记忆
bioRxiv : the preprint server for biology
|June 12, 2025
概括
性结肠炎患者的肠干细胞保留了炎症的记忆. 这种表观遗传记忆为未来的伤害做好了准备,可能导致疾病复发.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 性结肠炎 (UC) 涉及肠道上皮损伤和修复功能受损,即使在炎症减弱后也会持续下去.
- 肠道干细胞 (ISCs) 可能保留表观遗传变化,这表明肠道中的长期表皮记忆.
- 以前炎症部位的UC复发表明,炎症性肠病 (IBD) 患者的ISC可能会获得持久的炎症记忆.
研究的目的:
- 调查UC患者的ISC是否会获得和保留先前炎症的持久表观遗传记忆.
- 描述结肠器官中这种保留记忆的分子和功能后果.
主要方法:
- 结肠器官来自UC患者的炎症和非炎症区域.
- 长期培养和染色质分析 (ATAC-seq) 用于分析表观遗传变化.
- 用炎症或损伤刺激对器官进行了重新挑战,以评估功能反应.
主要成果:
- 预先炎症的 (PI) 器官表现出与压力,修复和炎症相关的独特可访问的色素区域.
- 这些区域仍然可访问,表明原始状态而不是活跃的基因表达.
- PI有机体对重新挑战的反应得到了增强,包括伤口更快地关闭,但屏障功能和克隆原性降低.
结论:
- 人类ISC保留了基于染色体的炎症记忆,在没有免疫线索的情况下持续存在.
- 这种记忆塑造了未来对伤害的反应,可能有助于适应,但也会导致UC复发.
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