Single-cell chromatin accessibility landscape in kidney identifies additional cell-of-origin in heterogenous papillary renal cell carcinoma

• Type of Material: Article
• Authors: Qi Wang, Medical School of Nanjing University; Yang Zhang, Medical School of Nanjing University; Bolei Zhang, Nanjing University of Post and TeleCommunications; Yao Fu, Medical School of Nanjing University; Xiaozhi Zhao, Medical School of Nanjing University; Jing Zhang, Medical School of Nanjing University; Ke Zuo, Medical School of Nanjing University; Yuexian Xing, Medical School of Nanjing University; Song Jiang, Medical School of Nanjing University; Zhaohui Qin, Emory University; Erguang Li, Medical School of Nanjing University; Hongqian Guo, Medical School of Nanjing University; Zhihong Liu, Medical School of Nanjing University; Jingping Yang, Medical School of Nanjing University
• Language: English
• Date: 2022-12-01
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-021-27660-3
• Title of Journal or Parent Work: Nature Communications
• Volume: 13
• Issue: 1
• Start Page: 31
• End Page: 31
• Grant/Funding Information: We are grateful to support from the National Natural Science Foundation of China (81500515, J.Y.), Natural Science Foundation of Jiangsu Province (BK20150591, J.Y.), Nanjing University and Emory University Collaborative Research Grants (NE2019003, J.Y.), the Fundamental Research Funds for the Central University (021114380172, J.Y.), Jiangsu Clinical Medical Center (innovation platform, YXZXA2016003, Z.L.), The Open Project of Jiangsu Biobank of Clinical Resources (JSRB2021-01, J.Y.).
• Keywords: Kidney; Carcinoma, Papillary; Humans; Carcinoma, Renal Cell; Biomarkers, Tumor; DNA-Binding Proteins; Kidney Neoplasms; Epigenomics; Molecular Medicine; Chromatin; Transcription Factors
• Research Categories: Health Sciences, Public Health; Biology, Biostatistics; Computer Science; Health Sciences, Pathology

Abstract

Papillary renal cell carcinoma (pRCC) is the most heterogenous renal cell carcinoma. Patient survival varies and no effective therapies for advanced pRCC exist. Histological and molecular characterization studies have highlighted the heterogeneity of pRCC tumours. Recent studies identified the proximal tubule (PT) cell as a cell-of-origin for pRCC. However, it remains elusive whether other pRCC subtypes have different cell-of-origin. Here, by obtaining genome-wide chromatin accessibility profiles of normal human kidney cells using single-cell transposase-accessible chromatin-sequencing and comparing the profiles with pRCC samples, we discover that besides PT cells, pRCC can also originate from kidney collecting duct principal cells. We show pRCCs with different cell-of-origin exhibit different molecular characteristics and clinical behaviors. Further, metabolic reprogramming appears to mediate the progression of pRCC to the advanced state. Here, our results suggest that determining cell-of-origin and monitoring origin-dependent metabolism could potentially be useful for early diagnosis and treatment of pRCC.