软骨鱼类小斑猫鲨中具有低翻译活性的肾祖细胞的胚后维持。

Postembryonic Maintenance of Nephron Progenitor Cells with Low Translational Activity in the Chondrichthyan Scyliorhinus canicula.

作者信息

Lund-Ricard Yasmine, Calloch Julien, Glippa Virginie, Vandenplas Sam, Huysseune Ann, Witten P Eckhard, Morales Julia, Boutet Agnès

机构信息

Laboratory of Integrative Biology of Marine Models (LBI2M), Station Biologique, CNRS, Sorbonne Université, Roscoff, France.

Biology Department, Evolutionary Developmental Biology Group, Ghent University, Ghent, Belgium.

出版信息

J Am Soc Nephrol. 2025 Apr 1;36(4):571-586. doi: 10.1681/ASN.0000000558. Epub 2024 Nov 22.

DOI:10.1681/ASN.0000000558

PMID:39699552

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11975252/

Abstract

KEY POINTS

Unlike mammals, chondrichthyan species exhibit postembryonic nephrogenesis, where new nephrons are continuously added in the kidney. Nephron progenitor cells in catsharks display slow cycling property, akin to other somatic stem cells, indicating their potential for tissue renewal and regeneration. Molecular analysis suggests a potential link between protein synthesis rate and nephron progenitor cell maintenance.

BACKGROUND

While adult mammals are unable to grow new nephrons, cartilaginous fish kidneys display nephrogenesis throughout life. In this study, we investigated the molecular properties of nephron progenitor cells (NPCs) within the kidney of the catshark ().

METHODS

We used branched DNA hybridization to analyze markers expressed in catshark NPCs. Bromodesoxyuridine pulse-chase labeling was also performed to test whether NPCs are slow-cycling cells. To question the mechanisms allowing NPC maintenance in the catshark postembryonic kidney, we measured global protein synthesis rates using OP-puromycin incorporation. We also investigated the expression of two targets of the mammalian target of rapamycin pathway, an important signaling pathway for translation initiation.

RESULTS

We found that NPCs express molecular markers previously identified in mice and teleost embryonic NPCs, such as the transcription factors Six2, Pax2, and Wt1. At postembryonic stages, these NPCs are integrated into a specific nephrogenic area of the kidney and contain slow-cycling cells. We also evidenced that NPCs have lower protein synthesis levels than the differentiated cells present in forming nephrons. Such transition from low to high translation rates has been previously observed in several populations of vertebrate stem cells as they undergo differentiation. Finally, we reported the phosphorylation of two targets of the mammalian target of rapamycin pathway, p4E-BP1 and pS6K1, in catshark differentiated epithelial cells but not in the NPCs.

CONCLUSIONS

This first molecular analysis of NPCs in a chondrichthyan species indicates that translation rate increases in NPCs as they differentiate into epithelial cells of the nephron.

PODCAST

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摘要

关键点

与哺乳动物不同，软骨鱼类物种表现出胚胎后肾发生，即新的肾单位在肾脏中持续添加。猫鲨中的肾单位祖细胞表现出缓慢循环特性，类似于其他体细胞干细胞，表明它们具有组织更新和再生的潜力。分子分析表明蛋白质合成速率与肾单位祖细胞维持之间存在潜在联系。

背景

成年哺乳动物无法生成新的肾单位，而软骨鱼类的肾脏终生都有肾发生。在本研究中，我们调查了猫鲨（）肾脏中肾单位祖细胞（NPC）的分子特性。

方法

我们使用分支DNA杂交来分析猫鲨NPC中表达的标志物。还进行了溴脱氧尿苷脉冲追踪标记，以测试NPC是否为缓慢循环细胞。为了探究允许猫鲨胚胎后肾脏中NPC维持的机制，我们使用OP-嘌呤霉素掺入法测量了整体蛋白质合成速率。我们还研究了雷帕霉素靶蛋白途径的两个靶点的表达，该途径是翻译起始的重要信号通路。

结果

我们发现NPC表达先前在小鼠和硬骨鱼胚胎NPC中鉴定出的分子标志物，如转录因子Six2、Pax2和Wt1。在胚胎后阶段，这些NPC整合到肾脏的特定肾发生区域，并包含缓慢循环细胞。我们还证明，NPC的蛋白质合成水平低于正在形成的肾单位中存在的分化细胞。这种从低翻译速率到高翻译速率的转变先前在几个脊椎动物干细胞群体分化过程中已被观察到。最后，我们报道了雷帕霉素靶蛋白途径的两个靶点p4E-BP1和pS6K1在猫鲨分化上皮细胞中发生磷酸化，但在NPC中未发生。