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Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors

Matthew D Young1, Thomas J Mitchell1,2,3, Felipe A Vieira Braga1

  • 1Wellcome Sanger Institute, Hinxton CB10 1SA, UK.

Science (New York, N.Y.)
|August 11, 2018
PubMed

Insights

This study analyzed 72,501 kidney tumor and normal cell transcriptomes. Findings reveal Wilms tumors are aberrant fetal cells and adult kidney cancers match a specific proximal tubule cell type.

Area of Science:

  • Oncology
  • Genomics
  • Cell Biology

Background:

  • Messenger RNA (mRNA) defines cellular identity and function in human cancers.
  • Understanding tumor composition is crucial for diagnosing and treating kidney cancers.

Purpose of the Study:

  • To precisely identify the cellular identities and compositions of human kidney tumors.
  • To investigate the cellular origins of Wilms tumor and renal cell carcinoma.

Main Methods:

  • Single-cell RNA sequencing of 72,501 human renal tumors and normal tissues.
  • Comparative transcriptomic analysis to match tumor cells with normal cell types.
  • Analysis of tumor microenvironment composition and signaling pathways.

Main Results:

  • Wilms tumor cells were matched to specific fetal cell types, supporting the aberrant fetal cell hypothesis.
  • Adult renal cell carcinoma transcriptomes identified a canonical cancer profile matching a rare proximal convoluted tubular cell subtype.
  • Cancer-associated normal cells and a vascular endothelial growth factor (VEGF) signaling circuit were delineated within tumors.

Conclusions:

  • This study provides precise cellular identities for human kidney tumors.
  • Findings offer insights into the developmental origins of Wilms tumor and the cellular basis of adult renal cell carcinoma.

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