核核压缩机NCOR1和NCOR2引发了胸细胞信号,选择和迁移
Natalie A David1, Robin D Lee1, Rebecca S LaRue2
1Center for Immunology, Masonic Cancer Center, Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN 55455.
bioRxiv : the preprint server for biology
|October 9, 2023
概括
核受体核心压缩剂1 (NCOR1) 和NCOR2对于T细胞发育至关重要. 结合NCOR1和NCOR2的删除阻断了胸细胞的发育,改变了T细胞受体信号和选择.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- T细胞的发育涉及精确的基因调节,包括诱导和抑制.
- 转录因子利用核心压缩复合体与染色质重塑酶进行基因沉默.
- 核受体核心压缩剂1 (NCOR1) 和NCOR2 招募基因组脱乙酶来沉默目标基因.
研究的目的:
- 调查NCOR1和NCOR2在调节胸细胞发育中的作用.
- 为了确定NCOR1和NCOR2的更广泛的功能,超出NCOR1在胆小细胞存活中的之前已知的作用.
主要方法:
- 流细胞测量用于分析胸细胞群.
- 单细胞RNA测序提供了高分辨率的基因表达数据.
- 在小鼠 (Cd4-cre) 中使用条件基因删除来研究NCOR1和NCOR2的功能.
主要成果:
- 仅仅NCOR2的条件删除对胸细胞发育没有显著影响.
- 仅仅NCOR1的有条件删除具有适度的效果.
- 在Cd4-cre小鼠中,NCOR1和NCOR2的联合删除导致了DP到SP过渡的显著阻断.
- 结合NCOR1/2删除导致T细胞受体信号,BIM表达和负选择的增加.
- 观察到NF-κB,NUR77和MAPK通路的升级,影响了谱系承诺,TCR重组和胸细胞迁移.
结论:
- NCOR1和NCOR2的作用是组合的,可以调节多个阶段的胸细胞发育.
- NCOR1/2的联合作用对于适当的T细胞成熟至关重要.
- 对NCOR1/2的调节失调会影响T细胞受体信号传递,选择和血统承诺.
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