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

Apicobasal cell polarity loss is a founding event in epithelial-mesenchymal transition 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 singl...

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Bibliographic Details
Published in:eLife 2022-11, Vol.11
Main Authors: Chatterjee, Deeptiman, Costa, Caique Almeida Machado, Wang, Xian-Feng, Jevitt, Allison, Huang, Yi-Chun, Deng, Wu-Min
Format: Article
Language:English
Subjects:
Analysis
Animals
Cancer Biology
Carcinogenesis
Cell division
cell polarity
Cloning
collective cell invasion
Computational and Systems Biology
Cytoskeleton
Drosophila
Drosophila - genetics
Drosophila Proteins - metabolism
Ectopic expression
follicle cells
Gene expression
Genetic aspects
Insects
Keap1-Nrf2
Kelch-Like ECH-Associated Protein 1 - genetics
Kelch-Like ECH-Associated Protein 1 - metabolism
Mesenchyme
Neoplasms
NF-E2-Related Factor 2 - genetics
NF-E2-Related Factor 2 - metabolism
Ovaries
Phenotypes
Plasticity
Polarity
RNA sequencing
scRNA-seq
Stem cells
Transcriptome
Transcriptomes
Transcriptomics
Tumorigenesis
Tumors
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Description
Summary:Apicobasal cell polarity loss is a founding event in epithelial-mesenchymal transition 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 ovaries, where inducing polarity-gene -knockdown (Lgl-KD) causes invasive multilayering of the follicular epithelia. Analyzing the integrated Lgl-KD and 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.80956