Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Meghan Ferguson; Kristina Petkau; Minjeong Shin; Anthony Galenza; David Fast; Edan Foley

doi:10.1242/dev.186106

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Meghan Ferguson, Kristina Petkau, Minjeong Shin, Anthony Galenza, David Fast, Edan Foley

Research output: Contribution to journal › Article › peer-review

15 Citations (SciVal)

Abstract

Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined the effects of commensal Lactobacillus species on homeostatic and tumorigenic stem cell proliferation in the female Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell divisions. In a wild-type midgut, L.brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, L.brevis-mediated proliferation causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that L.brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on division and maintenance of the intestinal progenitor compartment.

Original language	English
Pages (from-to)	1-20
Journal	Development (Cambridge, England)
Volume	148
Issue number	5
DOIs	https://doi.org/10.1242/dev.186106
Publication status	Published - 9 Mar 2021

Data Availability Statement

Gene expression data have been deposited to the NCBI Gene Expression Omnibus
database under accession number GSE138555

Funding

This work was supported by a grant from the Canadian Institutes of Health Research (PJT 159604). A.G. and D.F. have funding support through Natural Sciences and Engineering Research Council of Canada scholarships. M.F. is funded by an Alberta Innovates Graduate Student Scholarship

Keywords

Animals
Animals, Genetically Modified/metabolism
Anti-Bacterial Agents/pharmacology
Cell Adhesion
Cell Differentiation
Cell Lineage
Cell Proliferation
Cell Transformation, Neoplastic/drug effects
Down-Regulation
Drosophila/metabolism
Drosophila Proteins/deficiency
Integrins/metabolism
Intestines/cytology
Levilactobacillus brevis/drug effects
Receptors, Notch/deficiency
Stem Cells/cytology

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10.1242/dev.186106

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title = "Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine",

abstract = "Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined the effects of commensal Lactobacillus species on homeostatic and tumorigenic stem cell proliferation in the female Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell divisions. In a wild-type midgut, L.brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, L.brevis-mediated proliferation causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that L.brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on division and maintenance of the intestinal progenitor compartment.",

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author = "Meghan Ferguson and Kristina Petkau and Minjeong Shin and Anthony Galenza and David Fast and Edan Foley",

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doi = "10.1242/dev.186106",

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AU - Ferguson, Meghan

AU - Petkau, Kristina

AU - Shin, Minjeong

AU - Galenza, Anthony

AU - Fast, David

AU - Foley, Edan

PY - 2021/3/9

Y1 - 2021/3/9

N2 - Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined the effects of commensal Lactobacillus species on homeostatic and tumorigenic stem cell proliferation in the female Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell divisions. In a wild-type midgut, L.brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, L.brevis-mediated proliferation causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that L.brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on division and maintenance of the intestinal progenitor compartment.

AB - Microbial factors influence homeostatic and oncogenic growth in the intestinal epithelium. However, we know little about immediate effects of commensal bacteria on stem cell division programs. In this study, we examined the effects of commensal Lactobacillus species on homeostatic and tumorigenic stem cell proliferation in the female Drosophila intestine. We identified Lactobacillus brevis as a potent stimulator of stem cell divisions. In a wild-type midgut, L.brevis activates growth regulatory pathways that drive stem cell divisions. In a Notch-deficient background, L.brevis-mediated proliferation causes rapid expansion of mutant progenitors, leading to accumulation of large, multi-layered tumors throughout the midgut. Mechanistically, we showed that L.brevis disrupts expression and subcellular distribution of progenitor cell integrins, supporting symmetric divisions that expand intestinal stem cell populations. Collectively, our data emphasize the impact of commensal microbes on division and maintenance of the intestinal progenitor compartment.

KW - Animals

KW - Animals, Genetically Modified/metabolism

KW - Anti-Bacterial Agents/pharmacology

KW - Cell Adhesion

KW - Cell Differentiation

KW - Cell Lineage

KW - Cell Proliferation

KW - Cell Transformation, Neoplastic/drug effects

KW - Down-Regulation

KW - Drosophila/metabolism

KW - Drosophila Proteins/deficiency

KW - Integrins/metabolism

KW - Intestines/cytology

KW - Levilactobacillus brevis/drug effects

KW - Receptors, Notch/deficiency

KW - Stem Cells/cytology

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DO - 10.1242/dev.186106

M3 - Article

C2 - 33593820

SN - 0950-1991

VL - 148

SP - 1

EP - 20

JO - Development (Cambridge, England)

JF - Development (Cambridge, England)

IS - 5

ER -

Differential effects of commensal bacteria on progenitor cell adhesion, division symmetry and tumorigenesis in the Drosophila intestine

Abstract

Data Availability Statement

Funding

Keywords

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