通过核酸细胞计测识别星细胞调节剂
Iain C Clark1,2,3, Michael A Wheeler1,4, Hong-Gyun Lee1
1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nature
|January 4, 2023
概括
研究人员开发了FIND-seq, 这是一种用于研究多发性硬化症等中枢神经系统疾病的新方法. 这项技术确定了涉及NR3C2和NCOR2的机制,限制了有害的星球细胞反应,提供了潜在的治疗点.
科学领域:
- 神经科学
- 免疫学
- 基因组学
背景情况:
- 多发性硬化 (MS) 是一种慢性中枢神经系统 (CNS) 炎症性疾病.
- 星球细胞,中枢神经系统的质细胞,有助于MS的发病,但由于缺乏独特的表面标记物,它们的子集不明.
- 识别和分析罕见的致病性星球细胞子集对于了解多发性硬化和开发治疗方法至关重要.
研究的目的:
- 开发一种用于罕见和特定细胞群的高通量转录组分析的新方法.
- 研究 X-box 结合蛋白 1 (XBP1) 在多发性硬化症患者的星球细胞反应中的作用及其动物模型.
- 在MS中发现致病性星球细胞反应的新调节剂.
主要方法:
- 通过核酸检测和测序 (FIND-seq) 对细胞进行定向检查:一种微流体方法,结合细胞封装,PCR和单细胞转录组分类.
- 用FIND-seq研究XBP1调节的小鼠自身免疫脑炎 (EAE) 和人类多发性硬化样本.
- 整合条件淘汰的小鼠,CRISPR-Cas9遗传乱,以及大量/单细胞RNA测序.
主要成果:
- 在单细胞分辨率下,FIND-seq成功实现了罕见细胞的深度转录组分析.
- 确定了NR3C2核受体及其核心压缩器NCOR2之前未知的作用.
- 证明NR3C2和NCOR2限制了XBP1驱动的致病性星球细胞反应.
结论:
- FIND-seq是一个强大的工具,用于调查以前无法访问的罕见细胞子集.
- 该NR3C2-NCOR2通路代表了一种新的,可针对性治疗的机制,用于限制多发性硬化症患者的致病性星球细胞活动.
- 这项研究有助于更好地了解星球细胞异质性及其在中枢神经系统炎症疾病中的作用.
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