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比较非洲爪蟾原肾和小鼠后肾肾单位的细胞多样性。

A comparative study of cellular diversity between the Xenopus pronephric and mouse metanephric nephron.

机构信息

Department of Pediatrics, Pediatric Research Center, McGovern Medical School, UTHealth Houston, Houston, Texas, USA.

Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

出版信息

Kidney Int. 2023 Jan;103(1):77-86. doi: 10.1016/j.kint.2022.07.027. Epub 2022 Aug 31.

Abstract

The kidney is an essential organ that ensures bodily fluid homeostasis and removes soluble waste products from the organism. Nephrons, the functional units of the kidney, comprise a blood filter, the glomerulus or glomus, and an epithelial tubule that processes the filtrate from the blood or coelom and selectively reabsorbs solutes, such as sugars, proteins, ions, and water, leaving waste products to be eliminated in the urine. Genes coding for transporters are segmentally expressed, enabling the nephron to sequentially process the filtrate. The Xenopus embryonic kidney, the pronephros, which consists of a single large nephron, has served as a valuable model to identify genes involved in nephron formation and patterning. Therefore, the developmental patterning program that generates these segments is of great interest. Prior work has defined the gene expression profiles of Xenopus nephron segments via in situ hybridization strategies, but a comprehensive understanding of the cellular makeup of the pronephric kidney remains incomplete. Here, we carried out single-cell mRNA sequencing of the functional Xenopus pronephric nephron and evaluated its cellular composition through comparative analyses with previous Xenopus studies and single-cell mRNA sequencing of the adult mouse kidney. This study reconstructs the cellular makeup of the pronephric kidney and identifies conserved cells, segments, and associated gene expression profiles. Thus, our data highlight significant conservation in podocytes, proximal and distal tubule cells, and divergence in cellular composition underlying the capacity of each nephron to remove wastes in the form of urine, while emphasizing the Xenopus pronephros as a model for physiology and disease.

摘要

肾脏是一个重要的器官,它确保了体内液体的平衡,并从机体中清除可溶性的废物。肾单位是肾脏的功能单位,包括一个血液过滤器肾小球或球囊,以及一个上皮小管,它处理来自血液或体腔的滤液,并选择性地重吸收溶质,如糖、蛋白质、离子和水,将废物排出尿液中。编码转运体的基因呈节段性表达,使肾单位能够依次处理滤液。非洲爪蟾胚胎肾,前肾,由一个大的肾单位组成,一直是一个很有价值的模型,用于识别参与肾单位形成和模式形成的基因。因此,产生这些节段的发育模式程序非常有趣。先前的工作已经通过原位杂交策略定义了非洲爪蟾肾单位的基因表达谱,但对前肾的细胞组成仍不完全了解。在这里,我们对功能性非洲爪蟾前肾单位进行了单细胞 mRNA 测序,并通过与先前的非洲爪蟾研究和成年小鼠肾脏的单细胞 mRNA 测序进行比较分析,评估了其细胞组成。这项研究重建了前肾的细胞组成,并确定了保守的细胞、节段和相关的基因表达谱。因此,我们的数据强调了足细胞、近端和远端小管细胞的显著保守性,以及每个肾单位去除尿液形式废物的能力的细胞组成的差异,同时强调了非洲爪蟾前肾作为生理和疾病模型的重要性。

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