表观遗传开关重塑了表皮原生细胞的特征,并驱动了hidradenitis suppurativa炎症的炎症病变发生
Lin Jin1,2,3, Yunjia Chen4, Suhail Muzaffar2,3
1Center for Epigenomics and Translational Research in Inflammatory Skin Diseases, Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294.
概括
补腺炎 (HS) 涉及皮肤原生细胞变得致病,导致炎症. 表观遗传变化和特定的基因表达驱动HS,提供新的治疗点.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 补腺炎 (HS) 是一种慢性炎症性皮肤疾病,其机制尚不清楚.
- 表皮细胞功能障碍与HS的发病有关,但特定的细胞和分子驱动因素仍然不清楚.
研究的目的:
- 为了研究上皮原生细胞在HS中的作用.
- 阐明驱动HS病变的分子和表观遗传机制.
- 为了确定HS的潜在治疗点.
主要方法:
- 从HS和健康皮肤上皮质干细胞/原生细胞中对基因表达和表观基因组数据集的比较分析.
- 细胞分化轨迹重建和CellChat建模以确定HS特异性细胞群.
- 编辑CRISPR/Cas9基因和制药抑制以准已识别的途径.
主要成果:
- 在HS的基底原生细胞中,表现出改变的血统限制,形成致病性角质细胞克隆.
- HS角质细胞表现出与细胞循环,DNA修复,细胞粘附和染色质重塑相关的独特基因特征.
- 一个表达S100A7/8/9和KRT6的新型HS特异性角质细胞群触发了炎症级联.
- S100A8在调节HS角质细胞中的染色质可访问性方面发挥作用.
- 全基因组的染色质重新连接和转录因子切换介导HS转录特征.
- 在HS基底细胞中确定了临床相关的炎症增强剂及其相关的转录因子.
- 准S100A增强剂或IRF3降低HS相关的炎症调节剂.
结论:
- 皮肤上原始细胞的可塑性是HS病变的关键特征.
- 表观遗传失调,包括染色质重塑和增强剂活性,显著导致HS.
- 针对特定的S100A增强剂或IRF3是HS的有希望的治疗策略.
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