Integrative analysis of Paneth cell proteomic and transcriptomic data from intestinal organoids reveals functional processes dependent on autophagy.

Disease Models & Mechanisms
Emily J JonesT Korcsmáros

Abstract

Paneth cells are key epithelial cells that provide an antimicrobial barrier and maintain integrity of the small-intestinal stem cell niche. Paneth cell abnormalities are unfortunately detrimental to gut health and are often associated with digestive pathologies such as Crohn's disease or infections. Similar alterations are observed in individuals with impaired autophagy, a process that recycles cellular components. The direct effect of autophagy impairment on Paneth cells has not been analysed. To investigate this, we generated a mouse model lacking Atg16l1 specifically in intestinal epithelial cells, making these cells impaired in autophagy. Using three-dimensional intestinal organoids enriched for Paneth cells, we compared the proteomic profiles of wild-type and autophagy-impaired organoids. We used an integrated computational approach combining protein-protein interaction networks, autophagy-targeted proteins and functional information to identify the mechanistic link between autophagy impairment and disrupted pathways. Of the 284 altered proteins, 198 (70%) were more abundant in autophagy-impaired organoids, suggesting reduced protein degradation. Interestingly, these differentially abundant proteins comprised 116 proteins ...Continue Reading

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Citations

Jun 9, 2020·Frontiers in Cellular and Infection Microbiology·Ka-Yee Grace ChoiRobert E W Hancock
Nov 12, 2020·Cell Proliferation·Erpeng Yang, Jun Shen
Dec 21, 2020·Journal of Crohn's & Colitis·Martina PolettiTamas Korcsmaros
Feb 9, 2021·Trends in Cell Biology·Siamak Redhai, Michael Boutros
Jan 8, 2021·Tissue Engineering. Part C, Methods·Vera M PietersAlison P McGuigan

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Datasets Mentioned

BETA
PXD010940

Methods Mentioned

BETA
lipidation
reverse transcription PCR
structure-based predictions
PCR
electrophoresis
RNA-seq
pull-down
RNA assay
pulldown
chip

Software Mentioned

FIJI
RTA
FastQC
Progenesis QI
CASAVA
Percolator
DOMINE
bcl2fastq
Ensembl
ImageJ

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