外围单细胞的表观基因预定决定了它们对瘤微环境的转录反应
Máté Kiss1,2,3,4, Laszlo Halasz5,6, Eva Hadadi7,8,9
1Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium. mate.kiss@unige.ch.
Genome medicine
|July 23, 2025
概括
系统性炎症在它们到达瘤之前,在表观遗传上重新编程了外围单细胞. 这种预先条件塑造了它们促进瘤的功能,影响了癌症的进展.
科学领域:
- 免疫学 免疫学 免疫学
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 单细胞被招募到瘤中并被重新编程成促进瘤的细胞.
- 表观遗传学特征控制了对瘤微环境的转录反应.
- 目前尚不清楚系统信号是否在瘤透之前改变了外围单细胞表观基因组.
研究的目的:
- 调查由于系统性瘤信号而导致的外围单细胞的表观基因格局变化.
- 将表观遗传学变化与单细胞中的基因表达变化联系起来.
主要方法:
- 在小鼠瘤模型中使用全基因组测定染色质可访问性和基因组修饰 (H3K4me1,H3K4me3,H3K27ac).
- 综合表观基因和转录基因数据.
主要成果:
- 瘤诱导的炎症在表观遗传上具有先决条件的外围单细胞.
- 促进剂和增强剂发生了广泛的重塑,抑制了对干扰素有反应的元素,并建立了促炎信号模式.
- 重编程增强剂与持续的基因表达变化相关,并在循环单细胞中观察到促瘤基因原始化.
结论:
- 周围单细胞中与癌症相关的表观基因组重塑塑了它们与瘤相关的基因表达程序.
- 表观基因组在重定向单细胞功能以支持癌症进展方面发挥着关键作用.
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