昼夜调节器PER1通过抑制巨细胞的炎症信号来促进细胞重编程
Nobuko Katoku-Kikyo1,2, Seunghyun Lim1,3, Ce Yuan1,3
1Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota, United States of America.
PLoS biology
|December 4, 2023
概括
昼夜调节器PER1抑制炎症性巨细胞,增强细胞重编程,诱导神经元和干细胞. 这一发现将昼夜节律,炎症和重编程效率联系起来,影响未来的再生医学应用.
科学领域:
- 细胞生物学 细胞生物学
- 时间生物学 时间生物学
- 再生医学是一种再生医学.
背景情况:
- 循环节律调节基因表达和细胞分化.
- 昼夜调节在细胞重编程中的作用在很大程度上是未知的.
- 巨细胞可以影响细胞微环境.
研究的目的:
- 研究昼夜调节器在细胞重编程中的作用.
- 阐明PER1影响重新编程的机制.
- 探索巨细胞对重编程效率的影响.
主要方法:
- 病毒介导的重编程小鼠胚胎纤维细胞 (MEFs) 诱导神经元 (iNs) 和诱导多能干细胞 (iPSCs).
- 对基因表达的分析,包括Tnf等炎症标志物.
- 药理上抑制TNFα以评估其对重编程的影响.
主要成果:
- 通过抑制污染性巨细胞的炎症激活,PER1促进了病毒媒介的重编程.
- 转化病毒激活了巨细胞中的炎症基因 (Tnf),产生TNFα,抑制了重编程.
- PER1抑制了巨细胞的炎症反应,使重编程效率取决于一天中的时间.
- 在iPSC重编程中也观察到巨介导的抑制.
结论:
- 循环节调节器PER1通过抑制旁观者的炎症性巨细胞来增强细胞重编程.
- 炎症性巨细胞,特别是通过TNFα,抑制了MEFs重新编程到INs和iPSCs.
- 这项研究揭示了昼夜节律,巨细胞炎症和细胞重编程效率之间的机械联系.
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