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Author Notes:

Hongqian Guo, Email:dr.ghq@nju.edu.cn

J.Y. and Z.L. conceived of and designed the project. Q.W. and J.Y. wrote the manuscript with input from all other authors. Y.F., X.Z., K.Z., S.J., and H.G. prepared the paracancerous and tumor samples. Y.Z. generated scATAC-seq libraries and performed the immunofluorescence staining experiments; Q.W. designed the data analysis plan and optimized Cicero. Q.W. and B.Z. performed data analysis with assistance from Z.Q., E.L., Y.X., and J.Z.. All authors read and approved the final manuscript.

We thank Dr. Si Wei for insightful discussion and thank Ai Lin Chun for critically reading and editing the manuscript.

The authors have declared that no conflict of interest exists.

Subjects:

Research Funding:

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:

  • Biomarkers, Tumor
  • Carcinoma, Papillary
  • Carcinoma, Renal Cell
  • Chromatin
  • DNA-Binding Proteins
  • Epigenomics
  • Humans
  • Kidney
  • Kidney Neoplasms
  • Molecular Medicine
  • Transcription Factors

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

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Journal Title:

Nature Communications

Volume:

Volume 13, Number 1

Publisher:

, Pages 31-31

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2022

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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