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单细胞RNA测序揭示了糖尿病足的表皮分化受损和病理微环境

Yiling Liu^1,2, Peng Wang^1,2, Jingting Li²

¹Department of Burn and Wound Repair Surgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan 2 Road, Guangzhou 510080, China.

|March 5, 2025

概括

糖尿病足 (DFU) 由于明显的角质细胞亚型和促炎微环境,显示出受损的再表皮化. 这项研究确定了对DFU病理生理学的关键细胞参与者和途径,提供治疗点.

科学领域:

皮肤病学皮肤病学
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

糖尿病足 (DFU) 是一种复杂的糖尿病并发症,其病理生理学不清楚.
损伤的重新表皮化是DFU发展的一个关键问题.
单细胞RNA测序 (scRNA-seq) 提供了一个强大的工具,可以在分子水平上探索DFU.

研究的目的:

使用单细胞视角,全面分析DFU中受损再表皮化机制.
识别有助于DFU的新型细胞类型和分子配置文件.
阐明涉及DFU病理生理学的监管网络.

主要方法:

在正常人皮肤,急性伤口和DFU组织上进行scRNA-seq.
用伪时间和血统推断分析来分析表皮细胞轨迹.
进行了转录因子和细胞相互作用分析.
使用激光捕获显微镜与RNA测序 (LCM-seq) 和多重免疫组织化学相结合验证了关键发现.

主要成果:

确定了两个关键的角质细胞亚型,基底细胞 (BC-2) 和与糖尿病相关的角质细胞 (DAK),在DFU中增加和不活跃.
BC-2细胞参与细胞反应和细胞亡,具有下调的亲差异化因子.
达克细胞与葡萄糖平衡相关.
在DFU中检测到增加的亲炎性纤维细胞,血管细胞和T细胞,通过特定的途径影响表皮细胞命运,导致持续的炎症和受损的分化.

结论:

在DFU提供了表皮分化变化和监管网络的全面地图.
确定了BC-2和DAK角质细胞作为DFU病变发生的关键参与者.
突出了微环境在调节表皮平衡和DFU进展中的作用.
建议潜在的治疗目标,以改善DFU治疗结果.

关键词:

糖尿病足部糖尿病足部皮肤表皮的恒常性.再次上皮质化是重新上皮质化的.单细胞RNA测序的一个细胞.伤口微环境中的伤口.

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