在人类纤维化中解码肌纤维细胞起源
Christoph Kuppe1,2, Mahmoud M Ibrahim1,2,3, Jennifer Kranz2,4,5
1Division of Nephrology and Clinical Immunology, RWTH Aachen University, Aachen, Germany.
Nature
|November 11, 2020
概括
研究人员确定了纤维化的细胞起源, 揭示了特定的细胞群和纤维细胞群作为关键贡献者. 这一发现为开发针对肌纤维细胞的新型抗纤维治疗铺平了道路.
科学领域:
- 肝脏病学
- 细胞生物学
- 基因组学
背景情况:
- 纤维化是慢性病 (CKD) 进展的主要原因.
- 目前对纤维化的治疗选择有限,这突显了未得到满足的临床需求.
- 人类纤维化的细胞来源和痕形成细胞的调节尚不清楚.
研究的目的:
- 在健康和纤维化的人类脏中全面绘制细胞群.
- 在纤维化过程中确定负责肌纤维细胞分化的特定细胞类型.
- 发现抗纤维治疗的潜在治疗点.
主要方法:
- 人类细胞的单细胞RNA测序 (scRNA-seq).
- 在小鼠模型中的遗传命运跟踪和时间过程scRNA-seq.
- 在小鼠中使用测序 (ATAC-seq) 检测转化酶可访问的染色体.
- 人体纤维组织的空间转录.
主要成果:
- 高分辨率绘制人体中的生产细胞.
- 作为肌纤维细胞的主要来源,确定不同的细胞群和纤维细胞群.
- 细胞起源和肌纤维细胞分化途径的阐明.
- 发现NKD2作为肌纤维细胞特异性标.
结论:
- 细胞和纤维细胞是人类纤维化的关键细胞前体.
- 了解这些细胞动力学可以了解纤维化机制.
- 对于治疗纤维化而言,NKD2是一个有前途的治疗标.
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