Single-cell transcriptomics identifies Keap1-Nrf2 regulated collective invasion in a Drosophila tumor model
- Tulane University, United States
- 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.
Article and author information
Author details
Deeptiman Chatterjee
Funding
No external funding was received for this work.
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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Single-cell transcriptomics identifies Keap1-Nrf2 regulated collective invasion in a Drosophila tumor model
eLife 11:e80956.
https://doi.org/10.7554/eLife.80956
