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在膝关节骨关节炎期间,皮下脂肪的细胞和转录组多样性

Hayley Peters¹, Pratibha Potla², Jason S Rockel²

¹Division of Orthopaedics, Osteoarthritis Research Program, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.

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概括

这项研究揭示了皮下脂肪 (IFP) 细胞多样性和转录形状,确定IFP纤维细胞是膝关节关节炎 (KOA),性别和肥胖相关差异的关键参与者.

科学领域:

* 脂肪组织生物学
* 分子和系统生物学
* 骨科和类风湿病学

背景情况:

* 膝关节下脂肪 (IFP) 越来越多地被认为是膝关节恒温和疾病中的作用.
*了解IFP的细胞组成和转录基因格局对于阐明其对膝关节关节炎 (KOA) 的贡献至关重要.
*以前的研究缺乏对IFP的全面多原子分析,特别是与KOA,性别和肥胖相关的变化.

研究的目的:

*使用多原子方法全面绘制人类IFP的细胞和转录组多样性.
* 识别IFP中不同的细胞类型和子集,并描述它们的转录组特征.
*根据膝关节骨关节炎 (KOA) 状态,性别和肥胖程度,调查IFP细胞组成和转录组分的差异.

主要方法:

*来自21个IFP的82,924个核的单核RNA测序 (snRNA-seq) (6个健康对照组,15个KOA捐赠者).
*空间转录学用于解决细胞分布和通信网络.
*生物信息分析用于细胞子集群识别和纤维细胞多样性调查,并补充了肥胖相关差异的代谢学.

主要成果:

*识别多个纤维细胞,巨细胞,脂肪细胞和内皮细胞子集群,具有独特的转录组签名.
*空间转录学揭示了细胞类型分布和潜在的细胞-细胞通信通路.
*根据KOA状态,性别和肥胖度 (BMI) 在IFP纤维细胞中观察到显著的转录组差异. 代谢学进一步突出了肥胖个体纤维细胞的代谢变异.

结论:

* 这项研究提供了人类IFP的第一个全面的细胞和转录基因地图.
*IFP纤维细胞被确定为关键的细胞组件,表现出与KOA,性别和肥胖相关的转录和代谢变化.
*这些发现强调了IFP在膝关节病理生理学中的重要作用,并表明了潜在的治疗点.

关键词:

关节炎是一种关节炎.纤维细胞细胞.膝盖膝盖膝盖膝盖在骨关节炎是一种骨关节炎.风险因素风险因素

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