单个Th17细胞的代谢建模揭示了自身免疫的调节者
Allon Wagner1, Chao Wang2, Johannes Fessler3
1Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA 94720, USA; Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|July 3, 2021
概括
一个新的算法,指南针,分析单细胞代谢,揭示T助手17 (Th17) 细胞如何变得致病. 它将聚胺代谢确定为关键因素,为自身免疫性疾病提供新的治疗点.
科学领域:
- 免疫学
- 系统生物学
- 代谢工程
背景情况:
- 细胞代谢极大地影响免疫细胞的功能.
- 研究单个细胞的新陈代谢状态是具有挑战性的.
- 17 (Th17) 辅助T细胞表现出功能变异性,包括致病潜力.
研究的目的:
- 开发一种计算算法 (指南针) 用于表征细胞代谢状态.
- 将代谢状态与Th17细胞的功能变异性联系起来.
- 确定调节Th17致病性的代谢途径.
主要方法:
- 开发了集单细胞RNA测序和流量平衡分析的指南针算法.
- 应用指南针来分析Th17细胞的代谢状态.
- 使用代谢测定,遗传/化学干扰和中枢神经系统自身免疫的体内模型验证的结果.
主要成果:
- 在Th17细胞中,Compass发现了糖解与脂肪酸氧化之间的代谢转换.
- Th17病原性与氨酸和下游聚胺代谢相关.
- 扰乱多胺代谢抑制了Th17细胞因子,促进了调节性T细胞 (Treg) 标志物,并减轻了自身免疫性炎症.
结论:
- 指南针从单细胞RNA测序数据有效地表征细胞代谢状态.
- 聚胺代谢是Th17细胞致病性的关键决定因素.
- 针对多胺代谢是一种有前途的治疗策略,用于Th17介导的自身免疫疾病.
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