Open AccessHeterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease
Author(s) -
Qiong Li,
Yuchen Wang,
Wei Deng,
Yanna Liu,
Jiao Geng,
Ziyan Yan,
Fēi Li,
Binshen Chen,
Zhuolin Li,
Renfei Xia,
Wenli Zeng,
Rumin Liu,
Jiang Xu,
Fu Xiong,
ChinLee Wu,
Yun Miao
Publication year - 2021
Publication title -
theranostics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.689
H-Index - 97
ISSN - 1838-7640
DOI - 10.7150/thno.57220
Subject(s) - autosomal dominant polycystic kidney disease , cyst , biology , polycystic kidney disease , pkd1 , nephron , kidney , cell , transcriptome , clear cell , cell type , pathology , cancer research , microbiology and biotechnology , gene , renal cell carcinoma , endocrinology , medicine , gene expression , genetics
Rationale: 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. 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. 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.