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

Chatterjee, Deeptiman, Costa, Caique Almeida Machado, Wang, Xian-Feng, Jevitt, Allison, Huang, Yi-Chun, Deng, Wu-Min (November 2022) Single-cell transcriptomics identifies Keap1-Nrf2 regulated collective invasion in a Drosophila tumor model. eLife, 11. e80956. ISSN 2050-084X

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Abstract

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 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.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders organism description > animal > insect > Drosophila bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment diseases & disorders > neoplasms organism description > animal Investigative techniques and equipment > assays organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell polarity organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organism description > animal > insect organs, tissues, organelles, cell types and functions Investigative techniques and equipment > assays > RNA-seq bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:	Chatterjee, Deeptiman
Communities:	CSHL labs > Dos Santos lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 November 2022
Date Deposited:	09 Jan 2023 20:57
Last Modified:	11 Jan 2024 19:14
PMCID:	PMC9708074
URI:	https://repository.cshl.edu/id/eprint/40784

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