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E-MTAB-3649

ABSTRACT: Transcription profiling by high throughput sequencing of LoVo cells infected with Listeria for 24 hr compared to uninfected cells

OTHER RELATED OMICS DATASETS IN: PXD001805MSV000080750

PROVIDER: E-MTAB-3649 | ExpressionAtlas | 2019-05-14

REPOSITORIES: ExpressionAtlas

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			Action	DRS
	E-MTAB-3649-analysis-methods.tsv	Tabular
	E-MTAB-3649-analytics.tsv	Tabular
	E-MTAB-3649-analytics.tsv.undecorated	Tabular
	E-MTAB-3649-analytics.tsv.undecorated.unrounded	Tabular
	E-MTAB-3649-analytics.tsv.unrounded	Tabular

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Project description:Purpose: When we infect MDCK epithelial cells we low dosage of Listeria monocytogenes we observe that at late times (24 h) post infection that infected cells pertaining in infection foci get collectively extruded out of the epithelial monolayer forming a 3D mound. The formation of the infection mound results from the competition between two populations: the uninfected cells ("surrounders") that eventually squeeze and extrude the infected cells ("mounders"). Using RNA-Sequencing, we performed gene expression profiling for uninfected MDCK cells, cells infected for 24 h with Listeria monocytogenes at an MOI of 200 (both "mounders" and "surrounders") and cells sorted to infected ("mounders") or uninfected ("surrounders") populations after being infected for 24 h with Listeria monocytogenes. Our goal was to understand how transcriptional regulation leads to the collective extrusion of infected epithelial cells triggered by surrounding uninfected cells. Methods and Results: By analyzing the differentially expressed genes between all conditions we find a significant number of up- or down-regulated genes between all groups. Through pathway enrichemnet analysis we find that compared to cells not exposed to infection "mounders" showed significant downregulation in 31 genes related to tight junctions and ZO-1 was one of the key genes downregulated and to a lesser degree to pathways related to adherens junctions, focal adhesions and regulation of the actin cytoskeleton. "Surrounders" showed significant downregulation to genes related to actin cytoskeleton, to endocytosis to ahderens junctions and to a lesser degree focal adhesions and tight junctions. Especially "surrounders" and to a lesser degree "mounders" showed upregulation on IL-17 and NF-kB and TNF related signaling pathways, which underlines the fact that although "surrounders" are uninfected their distinct mechanical behavior might arise from cytokines released from "mounders" which impact crucially their phenotype. Interestingly "mounders" only showed additionally upregulation on DNA replication, cell cycle related pathways and ferroptosis suggesting that these cells might be undergoing some kind of stress response. Conclusions: Infection of MDCK epithelial cells with Listeria monocytogenes significantly alters the transcriptome of the infected host cells when those are examined 24 h post infection. Both infected and uninfected cells in an infected well show significant transcriptomic changes compared to uninfected cells but also compared to each other. Most importnantly innate immunity related pathways are singificanlty upregulated for un infected cells in an infected well and to a lesser degree for infected cells as compared to cells not exposed to infection.

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E-MTAB-3649

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