Single-cell transcriptomics identifies Keap1-Nrf2 regulated collective invasion in a Drosophila tumor model

  1. Deeptiman Chatterjee  Is a corresponding author
  2. Caique Almeida Machado Costa
  3. Xian-Feng Wang
  4. Allison Jevitt
  5. Yi-Chun Huang
  6. Wu-Min Deng  Is a corresponding author
  1. Tulane University, United States
  2. Oklahoma Medical Research Foundation, United States

Abstract

Apicobasal cell-polarity loss is a founding event in Epithelial-Mesenchymal Transition (EMT) and epithelial tumorigenesis, yet how pathological polarity loss links to plasticity remains largely unknown. To understand the mechanisms and mediators regulating plasticity upon polarity loss, we performed single-cell RNA sequencing of Drosophila ovaries, where inducing polarity-gene l(2)gl-knockdown (Lgl-KD) causes invasive multilayering of the follicular epithelia. Analyzing the integrated Lgl-KD and wildtype transcriptomes, we discovered the cells specific to the various discernible phenotypes and characterized the underlying gene expression. A genetic requirement of Keap1-Nrf2 signaling in promoting multilayer formation of Lgl-KD cells was further identified. Ectopic expression of Keap1 increased the volume of delaminated follicle cells that showed enhanced invasive behavior with significant changes to the cytoskeleton. Overall, our findings describe the comprehensive transcriptome of cells within the follicle-cell tumor model at the single-cell resolution and identify a previously unappreciated link between Keap1-Nrf2 signaling and cell plasticity at early tumorigenesis.

Data availability

Both raw and processed sequencing data is available at GSE175435. Code necessary to replicate the main findings of this study is available at https://github.com/chatterjee89/09-06-2022-RA-eLife-80956.

The following data sets were generated

Article and author information

Author details

  1. Deeptiman Chatterjee

    Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, United States
    For correspondence
    dchatterjee@tulane.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2752-4640
  2. Caique Almeida Machado Costa

    Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xian-Feng Wang

    Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Allison Jevitt

    Cancer and Cell Biology Department, Oklahoma Medical Research Foundation, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yi-Chun Huang

    Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Wu-Min Deng

    Department of Biochemistry and Molecular Biology, Tulane University, New Orleans, United States
    For correspondence
    wdeng7@tulane.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9098-9769

Funding

No external funding was received for this work.

Reviewing Editor

  1. Charles Farber, University of Virginia, United States

Version history

  1. Received: June 10, 2022
  2. Preprint posted: June 12, 2022 (view preprint)
  3. Accepted: November 1, 2022
  4. Accepted Manuscript published: November 2, 2022 (version 1)
  5. Version of Record published: November 29, 2022 (version 2)

Copyright

© 2022, Chatterjee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Deeptiman Chatterjee
  2. Caique Almeida Machado Costa
  3. Xian-Feng Wang
  4. Allison Jevitt
  5. Yi-Chun Huang
  6. Wu-Min Deng
(2022)
Single-cell transcriptomics identifies Keap1-Nrf2 regulated collective invasion in a Drosophila tumor model
eLife 11:e80956.
https://doi.org/10.7554/eLife.80956

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https://doi.org/10.7554/eLife.80956

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