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斑马鱼中肾干细胞的鉴定

Identification of renal stem cells in zebrafish.

作者信息

Yu Ting, Liu Xiaoliang, Tan Xiaoqin, Zhang Yunfeng, He Zhongwei, Yang Wenmin, Tian Tingting, Li Yan, Zhao Jinghong, Liu Chi

机构信息

Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China.

Department of Respiratory and Critical Care Medicine, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China.

出版信息

Sci Adv. 2025 Aug 22;11(34):eadx5296. doi: 10.1126/sciadv.adx5296.

DOI:10.1126/sciadv.adx5296
PMID:40845090
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12372851/
Abstract

Renal stem cells (RSC) hold great promise as kidney disease regenerative therapies. However, RSCs capable of regenerating de novo nephrons remain unidentified in vertebrates. Therefore, this study aimed to identify RSCs in zebrafish. Single-cell RNA sequencing revealed , , and as primary markers of zebrafish RSCs. Real-time imaging demonstrated that RSCs originated from -positive mesenchymal cells. Notably, photoconversion-based lineage tracing and serial transplantation assays revealed a unique RSC renewal process, characterized by a differentiation-proliferation-dedifferentiation mode. This process generates nephrons and nascent RSCs concurrently. In addition, precise Wnt signaling is key for RSC renewal and differentiation balance and directly activates expression to initiate renewal. This discovery establishes a foundation for the advancement of stem cell therapies for kidney diseases.

摘要

肾干细胞（RSC）作为肾脏疾病的再生疗法具有巨大潜力。然而，在脊椎动物中，能够再生全新肾单位的肾干细胞仍未被识别。因此，本研究旨在鉴定斑马鱼中的肾干细胞。单细胞RNA测序揭示了[此处原文缺失具体标记内容]、[此处原文缺失具体标记内容]和[此处原文缺失具体标记内容]作为斑马鱼肾干细胞的主要标记。实时成像表明肾干细胞起源于[此处原文缺失具体阳性细胞类型]阳性间充质细胞。值得注意的是，基于光转换的谱系追踪和连续移植试验揭示了一种独特的肾干细胞更新过程，其特征为分化 - 增殖 - 去分化模式。这一过程同时产生肾单位和新生肾干细胞。此外，精确的Wnt信号传导是肾干细胞更新和分化平衡的关键，并直接激活[此处原文缺失具体基因]表达以启动更新。这一发现为推进肾脏疾病的干细胞治疗奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/86a06ffc164f/sciadv.adx5296-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/36660c4288cd/sciadv.adx5296-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/b5904cd41e67/sciadv.adx5296-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/84e23d100501/sciadv.adx5296-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/cb135507f446/sciadv.adx5296-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/86a06ffc164f/sciadv.adx5296-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/36660c4288cd/sciadv.adx5296-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/b5904cd41e67/sciadv.adx5296-f5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/cb135507f446/sciadv.adx5296-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d363/12372851/86a06ffc164f/sciadv.adx5296-f8.jpg

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本文引用的文献

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Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration.肾近端小管分泌的 proenkephalin-A 作为肾脏再生的制动器发挥作用。
Nat Commun. 2023 Nov 7;14(1):7167. doi: 10.1038/s41467-023-42929-5.
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Regulation of adult stem cell quiescence and its functions in the maintenance of tissue integrity.
调节成体干细胞静止及其在维持组织完整性中的功能。
Nat Rev Mol Cell Biol. 2023 May;24(5):334-354. doi: 10.1038/s41580-022-00568-6. Epub 2023 Mar 15.
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Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2.肾间质细胞通过分泌前列腺素 E2 促进肾单位再生。
Elife. 2023 Jan 16;12:e81438. doi: 10.7554/eLife.81438.
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The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity.转录共激活因子 Eya1 通过与 REST 共抑制因子和 REST 结合序列相互作用发挥转录抑制活性，以维持肾祖细胞的特性。
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