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炎症诱导的表观遗传印记调节了肠道干细胞
Dongchang Zhao1, Visweswaran Ravikumar2, Tyler J Leach1
1Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Department of Internal Medicine, Houston, TX 77030, USA.
Cell stem cell
|September 4, 2024
概括
炎症会导致肠道干细胞 (ISC) 的长期表观遗传变化,甚至在炎症消失后,也会损害它们的再生能力. 这些细胞痕会影响未来的应激反应.
科学领域:
- 胃肠病学 胃肠病学
- 干细胞生物学 干细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肠道干细胞 (ISC) 对于肠道平衡和修复至关重要.
- 炎症对ISC功能和再生能力的长期影响尚不清楚.
研究的目的:
- 为了研究急性胃肠移植对宿主疾病 (GI GVHD) 如何影响Lgr5+ ISCs.
- 为了确定ISC中炎症诱导的适应是否会留下影响再生的持久性痕.
主要方法:
- 使用单细胞转录组学,有机体培养,代谢分析,表观基因组分析和体内模型.
- 在临床相关的急性GI GVHD模型中检查了Lgr5+ ISC.
主要成果:
- 在Lgr5+ISC中,炎症诱导了代谢变化,导致了酸盐的积累.
- 酸性积累表观遗传重新编程的ISC,降低它们的分化和再生能力ex vivo和in vivo.
- 即使在炎症消失后,ISCs也表现出受损的再生,这表明持续的不适应性影响.
结论:
- 炎症在ISCs上留下了一个持久的表观遗传印记.
- 这种印记降低了ISC的再生能力,并影响了它们适应未来挑战的能力.
- 了解这些持续的影响对于管理影响肠道的炎症状况至关重要.
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