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肌肉缺血通过NGFR和NGF促进质细胞和介质细胞之间的功能相互作用
Chiara Nicoletti1, Xiuqing Wei1, Usue Etxaniz1
1Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
iScience
|July 7, 2023
概括
化激活质细胞和Thy1/CD90+细胞,这些细胞通过NGF/NGFR相互作用. 这种相互作用最初促进了NMJ修复,但最终导致纤维化和对神经再生的敌对肌肉环境.
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 肌肉生理学 肌肉生理学
背景情况:
- 坐骨神经的截断导致肌肉缺血,影响神经肌肉结节 (NMJs).
- 了解细胞对脱皮的特异性反应对于开发治疗策略至关重要.
研究的目的:
- 通过使用scRNA-seq和snATAC-seq.来划分细胞类型特定的基因表达和色素可访问性模式.
- 调查NMJ修复失败早期阶段背后的细胞和分子机制.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 和单核ATAC测序 (snATAC-seq) 在坐骨神经截切后的不同时间点在骨肌肉上进行.
- 包括重组蛋白应用和共同培养在内的功能性测试被用于研究细胞-细胞通信.
主要成果:
- 化选择性激活质细胞和表达Thy1/CD90的介质细胞,与肌痛创伤反应不同.
- 表达NGF受体 (NGFR) 的质细胞位于NMJ附近,并与Thy1/CD90+细胞相互作用,这是NGF后退神的主要来源.
- NGF/NGFR信号传递促进了质细胞的扩散.
- 质细胞伪时间分析显示,分叉向脱差/专业化或神经再生受损,导致纤维化.
结论:
- 化激活的Thy1/CD90+细胞和质细胞之间的相互作用代表了NMJ修复的早期,失败的尝试.
- 这些相互作用有助于使无神肌肌肉转化为不有利于NMJ修复和再生的环境.
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