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通过综合空间和单细胞分析识别AKI到CKD过渡中的新型ECM重塑巨子集

Yi-Lin Zhang¹, Tao-Tao Tang¹, Bin Wang¹

¹Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, 210009, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|August 9, 2024

概括

巨细胞在急性损伤 (AKI) 过渡到慢性病 (CKD) 中发挥着关键作用. 这项研究揭示了不同的巨子集,包括新的细胞外矩阵重塑相关巨 (EAMs),为预防CKD提供了潜在的治疗点.

科学领域:

腎臟病學 (nephrology) 是一種醫學專業.
免疫学免疫学免疫学
翻译医学是一种翻译医学.

背景情况:

从急性损伤 (AKI) 过渡到慢性病 (CKD) 是一个重大的临床挑战.
巨细胞与AKI-to-CKD进展有关,但它们的异质性和动态作用尚不清楚.
了解巨细胞的行为对于开发向疗法至关重要.

研究的目的:

调查在AKI到CKD过渡期间巨细胞的时空异质性.
识别不同的巨细胞子集及其在纤维化和炎症中的作用.
探索预防CKD发展的潜在治疗点.

主要方法:

利用集成的单细胞RNA测序和空间转录组学.
采用了一种单边缺血-再输血损伤的小鼠模型 (AKI-to-CKD模型).
进行了伪时间分析,以界定巨细胞谱系差异化.

主要成果:

确定了两个不同的巨细胞系:亲修复性脏居民巨细胞和亲纤维性单细胞衍生的巨细胞.
发现了一种新的巨细胞子集,即细胞外矩阵重塑相关的巨细胞 (EAMs),起源于单细胞.
EAMs在空间上与纤维细胞相关,并通过胰岛素样生长因子 (IGF) 信号传递进行通信,促进纤维化.
观察到AKI后巨细胞的明显的时间透峰值.

结论:

描述了AKI到CKD过渡中的巨异质性的时空动态.
突出了EAM在纤维化中的关键作用.
EAMs是缓解CKD进展的有希望的治疗目标.

关键词:

艾基 (AKI) 是一个人.在CKD中,它是最重要的.巨细胞是一个巨细胞.一个单细胞RNA-seqq.空间的文字转录体.

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