Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney Disease
Kidney Single-Cell Atlas Reveals Myeloid Heterogeneity in Progression and Regression of Kidney Disease
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DOI：
10.1681/asn.2020060806
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发表时间：
2020-12-01
影响因子：
13.6
通讯作者：
Denby, Laura
中科院分区：
文献类型：
--
作者：
Conway, Bryan R.;O'Sullivan, Eoin D.;Denby, Laura
背景髓系细胞亚群在肾损伤和器官自身修复能力受限中的作用知之甚少。仅基于表面标志物使用流式细胞术表征这些细胞可能无法提供完整的表型图。定义这些细胞在单细胞，transcriptomic水平可以揭示骨髓异质性的进展和回归的kidney diseases.Methods集成液滴和板为基础的单细胞RNA测序中使用的小鼠，可逆的，单侧输尿管梗阻模型，解剖在单细胞水平的transcriptomic景观在肾损伤和纤维化的决议。配对血液交换追踪了招募到受损肾脏的单核细胞的命运。结果使用转录组学生成的肾脏单细胞图谱显示，在损伤和修复期间，肾细胞类型的比例和基因表达发生了显着变化。传统的流式细胞术标记物无法识别12个骨髓细胞亚群。损伤后早期招募到肾脏的单核细胞迅速采取表达Arg 1的促炎症、促纤维化表型，然后转变为在损伤晚期积聚的Ccr21巨噬细胞。相反，一个novelMmp121巨噬细胞亚群的行为在repair.Conclusions互补技术确定了新的髓系亚型，在单细胞中的转录组学的基础上，代表治疗目标，以抑制进展或促进肾脏疾病的消退。
Background Little is known about the roles ofmyeloid cell subsets in kidney injury and in the limited ability of the organ to repair itself. Characterizing these cells based only on surfacemarkers using flow cytometry might not provide a full phenotypic picture. Defining these cells at the single-cell, transcriptomic level could reveal myeloid heterogeneity in the progression and regression of kidney disease.Methods Integrated droplet- and plate-based single-cell RNA sequencing were used in the murine, reversible, unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single-cell level during renal injury and the resolution of fibrosis. Paired blood exchange tracked the fate of monocytes recruited to the injured kidney.Results A single-cell atlas of the kidney generated using transcriptomics revealed marked changes in the proportion and gene expression of renal cell types during injury and repair. Conventional flow cytometry markers would not have identified the 12myeloid cell subsets. Monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1, before transitioning to become Ccr21 macrophages that accumulate in late injury. Conversely, a novelMmp121macrophage subset acts during repair.Conclusions Complementary technologies identified novel myeloid subtypes, based on transcriptomics in single cells, that represent therapeutic targets to inhibit progression or promote regression of kidney disease.