Theranostics 2021; 11(20):10064-10073. doi:10.7150/thno.57220 This issue Cite

Research Paper

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

Qiong Li1*, Yuchen Wang1*, Wenfeng Deng1*, Yanna Liu2, Jian Geng3, Ziyan Yan1, Fei Li4, Binshen Chen5, Zhuolin Li6, Renfei Xia1, Wenli Zeng1, Rumin Liu1, Jian Xu1, Fu Xiong7, Chin-Lee Wu8✉, Yun Miao1✉

1. Department of Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou, China.
2. Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
3. Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
4. Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
5. Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
6. Guangzhou Saliai Stem Cell Science and Technology Company Limited, Guangzhou, China.
7. Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
8. Departments of Urology and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, U.S.A.
* These authors contributed equally to this work.

Citation:
Li Q, Wang Y, Deng W, Liu Y, Geng J, Yan Z, Li F, Chen B, Li Z, Xia R, Zeng W, Liu R, Xu J, Xiong F, Wu CL, Miao Y. Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease. Theranostics 2021; 11(20):10064-10073. doi:10.7150/thno.57220. https://www.thno.org/v11p10064.htm
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Abstract

Graphic abstract

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.

Keywords: ADPKD, Single-cell transcriptomics, Heterogeneity


Citation styles

APA
Li, Q., Wang, Y., Deng, W., Liu, Y., Geng, J., Yan, Z., Li, F., Chen, B., Li, Z., Xia, R., Zeng, W., Liu, R., Xu, J., Xiong, F., Wu, C.L., Miao, Y. (2021). Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease. Theranostics, 11(20), 10064-10073. https://doi.org/10.7150/thno.57220.

ACS
Li, Q.; Wang, Y.; Deng, W.; Liu, Y.; Geng, J.; Yan, Z.; Li, F.; Chen, B.; Li, Z.; Xia, R.; Zeng, W.; Liu, R.; Xu, J.; Xiong, F.; Wu, C.L.; Miao, Y. Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease. Theranostics 2021, 11 (20), 10064-10073. DOI: 10.7150/thno.57220.

NLM
Li Q, Wang Y, Deng W, Liu Y, Geng J, Yan Z, Li F, Chen B, Li Z, Xia R, Zeng W, Liu R, Xu J, Xiong F, Wu CL, Miao Y. Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease. Theranostics 2021; 11(20):10064-10073. doi:10.7150/thno.57220. https://www.thno.org/v11p10064.htm

CSE
Li Q, Wang Y, Deng W, Liu Y, Geng J, Yan Z, Li F, Chen B, Li Z, Xia R, Zeng W, Liu R, Xu J, Xiong F, Wu CL, Miao Y. 2021. Heterogeneity of cell composition and origin identified by single-cell transcriptomics in renal cysts of patients with autosomal dominant polycystic kidney disease. Theranostics. 11(20):10064-10073.

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