失去TET2和TET3会破坏小肠的分化和恒常性
Ihab Ansari1, Llorenç Solé-Boldo2, Meshi Ridnik1
1Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University Medical School, Jerusalem, Israel.
Nature communications
|July 6, 2023
概括
平素2和3 (TET2/3) 对于维持肠道平衡至关重要. 它们在小鼠体内不存在会破坏细胞平衡,改变DNA甲基化,并影响肠道健康.
科学领域:
- 表观遗传学和基因组学
- 胃肠道学和发育生物学
背景情况:
- 已知TET2/3酶对表观遗传调节和在小鼠发育中的作用.
- 它们在肠道细胞分化和组织平衡中的特定功能尚不清楚.
研究的目的:
- 调查TET2/3在肠上皮细胞分化和恒常性中的作用.
- 阐明肠道中TET2/3功能背后的分子机制.
主要方法:
- 在小鼠肠道上皮细胞中切除TET2 / 3.
- 分析肠道组织学,细胞群 (帕内斯,塔夫特,肠内分泌细胞).
- 在增强剂上进行DNA甲基化分析.
- 药理上抑制DNA甲基化.
- 微生物组分析和炎症反应的评估.
主要成果:
- 除TET2/3导致严重的肠道平衡失衡,导致帕内斯细胞的损失和改变的Tuft/肠内分泌细胞数量.
- 主要的DNA甲基化变化发生在与细胞命运转录因子和效应基因相关的增强剂中.
- 药理学DNA甲基化抑制部分挽救了细胞和甲基化缺陷.
- 失去TET2/3改变了肠道微生物组,增加了对炎症的易感性.
结论:
- TET2/3对于建立和维持肠道密室平衡至关重要.
- 由TET2/3调解的DNA去甲基化对于正常的细胞分化和肠道功能至关重要.
- 失去TET2/3会影响肠道微生物群,并导致炎症.
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