Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease

单细胞转录组学鉴定常染色体显性多囊肾病患者肾囊肿的细胞组成和来源的异质性

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作者:Qiong Li, Yuchen Wang, Wenfeng Deng, Yanna Liu, Jian Geng, Ziyan Yan, Fei Li, Binshen Chen, Zhuolin Li, Renfei Xia, Wenli Zeng, Rumin Liu, Jian Xu, Fu Xiong, Chin-Lee Wu, Yun Miao

Conclusion

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.

Methods

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.

Results

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.

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