Li Qiong, Wang Yuchen, Deng Wenfeng, Liu Yanna, Geng Jian, Yan Ziyan, Li Fei, Chen Binshen, Li Zhuolin, Xia Renfei, Zeng Wenli, Liu Rumin, Xu Jian, Xiong Fu, Wu Chin-Lee, Miao Yun
Department of Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Theranostics. 2021 Nov 1;11(20):10064-10073. doi: 10.7150/thno.57220. eCollection 2021.
Renal cysts in patients with autosomal dominant polycystic kidney disease (ADPKD) can originate from any nephron segments, including proximal tubules (PT), the loop of Henle (LOH), distal tubules (DT), and collecting ducts (CD). Previous studies mostly used limited cell markers and failed to identify cells negative for these markers. Therefore, the cell composition and origin of ADPKD cyst are still unclear, and mechanisms of cystogenesis of different origins await further exploration. We performed single-cell RNA sequencing for the normal kidney tissue and seven cysts derived from superficial or deep layers of the polycystic kidney from an ADPKD patient. Twelve cell types were identified and analyzed. We found that a renal cyst could be derived either from CD or both PT and LOH. Gene set variation analysis (GSVA) showed that epithelial mesenchymal transition (EMT), TNFA signaling via the NFKB pathways, and xenobiotic metabolism were significantly activated in PT-derived cyst epithelial cells while robust expression of genes involved in G2M Checkpoint, mTORC1 signaling, E2F Targets, MYC Targets V1, MYC Targets V2 were observed in CD-derived cells. Our results revealed that a single cyst could originate from CD or both PT and LOH, suggesting heterogeneity of polycystic composition and origin. Furthermore, cyst epithelial cells with different origins have different gene set activation.
常染色体显性多囊肾病（ADPKD）患者的肾囊肿可起源于任何肾单位节段，包括近端小管（PT）、髓袢（LOH）、远端小管（DT）和集合管（CD）。以往的研究大多使用有限的细胞标志物，未能识别出对这些标志物呈阴性的细胞。因此，ADPKD囊肿的细胞组成和起源仍不清楚，不同起源的囊肿发生机制有待进一步探索。我们对一名ADPKD患者的正常肾组织以及从多囊肾表层或深层获取的7个囊肿进行了单细胞RNA测序。鉴定并分析了12种细胞类型。我们发现肾囊肿可能起源于集合管，也可能起源于近端小管和髓袢。基因集变异分析（GSVA）显示，在起源于近端小管的囊肿上皮细胞中，上皮-间质转化（EMT）、通过NFKB途径的TNFA信号传导和外源性物质代谢显著激活，而在起源于集合管的细胞中观察到参与G2M检查点、mTORC1信号传导、E2F靶标、MYC靶标V1、MYC靶标V2的基因强烈表达。我们的结果表明，单个囊肿可能起源于集合管，也可能起源于近端小管和髓袢，提示多囊的组成和起源具有异质性。此外，不同起源的囊肿上皮细胞具有不同的基因集激活情况。
