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单细胞分析发育中的小鼠肾脏,深入了解标记基因表达和配体-受体相互作用。

Single cell analysis of the developing mouse kidney provides deeper insight into marker gene expression and ligand-receptor crosstalk.

机构信息

Department of Anatomy & Neuroscience, University of Melbourne, Parkville, Victoria 3010, Australia

Cell Biology, Murdoch Children's Research Institute, Flemington Rd, Parkville, Victoria 3052, Australia.

出版信息

Development. 2019 Jun 12;146(12):dev178673. doi: 10.1242/dev.178673.

Abstract

Recent advances in the generation of kidney organoids and the culture of primary nephron progenitors from mouse and human have been based on knowledge of the molecular basis of kidney development in mice. Although gene expression during kidney development has been intensely investigated, single cell profiling provides new opportunities to further subsect component cell types and the signalling networks at play. Here, we describe the generation and analysis of 6732 single cell transcriptomes from the fetal mouse kidney [embryonic day (E)18.5] and 7853 sorted nephron progenitor cells (E14.5). These datasets provide improved resolution of cell types and specific markers, including subdivision of the renal stroma and heterogeneity within the nephron progenitor population. Ligand-receptor interaction and pathway analysis reveals novel crosstalk between cellular compartments and associates new pathways with differentiation of nephron and ureteric epithelium cell types. We identify transcriptional congruence between the distal nephron and ureteric epithelium, showing that most markers previously used to identify ureteric epithelium are not specific. Together, this work improves our understanding of metanephric kidney development and provides a template to guide the regeneration of renal tissue.

摘要

近年来,基于对小鼠肾脏发育分子基础的了解,人们在肾脏类器官的生成和从鼠和人源分离的原代肾小体祖细胞培养方面取得了进展。尽管对肾脏发育过程中的基因表达进行了深入研究,但单细胞分析为进一步细分组成细胞类型和发挥作用的信号网络提供了新的机会。在这里,我们描述了从胎鼠肾脏(胚胎日(E)18.5)中生成和分析 6732 个单细胞转录组和从分离的肾小体祖细胞(E14.5)中分析 7853 个单细胞转录组。这些数据集提供了对细胞类型和特定标记物的分辨率的提高,包括肾基质的细分和肾小体祖细胞群体内的异质性。配体-受体相互作用和通路分析揭示了细胞区室之间的新串扰,并将新的途径与肾小体和输尿管上皮细胞类型的分化联系起来。我们发现远曲小管和输尿管上皮之间存在转录一致性,表明以前用于鉴定输尿管上皮的大多数标记物都不具有特异性。总之,这项工作增进了我们对后肾发育的理解,并为肾脏组织的再生提供了指导模板。

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