Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from Paneth cells isolated from mice on calorie restricted or ad libitum diet

ABSTRACT: Paneth cells recide in the intestinal crypt bottom and are part of the innate immunity and of the intestinal stem cell niche. We used microarrays to detail the global changes in gene expression following reduced calorie intake. Mice were kept on ad libitum or calorie restricted (60% of calories of ad libitum) diets for 4-7 weeks and paneth cells were isolated using flowcytometry

ORGANISM(S): Mus musculus

SUBMITTER: Pekka Katajisto

PROVIDER: E-GEOD-37209 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake.

Yilmaz Ömer H ÖH Katajisto Pekka P Lamming Dudley W DW Gültekin Yetis Y Bauer-Rowe Khristian E KE Sengupta Shomit S Birsoy Kivanc K Dursun Abdulmetin A Yilmaz V Onur VO Selig Martin M Nielsen G Petur GP Mino-Kenudson Mari M Zukerberg Lawrence R LR Bhan Atul K AK Deshpande Vikram V Sabatini David M DM

Nature 20120601 7404

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mT ...[more]

PMID: 22722868

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Project description:Crohn’s disease (CD) is associated with multiple Paneth cell dysfunctions such as altered antimicrobial secretion that relies on autophagy - an essential process controlling the turnover of cellular components. Genome-wide association studies have linked CD to mutations in the ATG16l1 gene, encoding an important component of the autophagy machinery. Patients carrying the ATG16l1 CD risk allele have Paneth cell abnormalities, as reproduced in Atg16l1-deficient mouse models. However, the direct effect of the ATG16L1-deficiency and autophagy-impairment in Paneth cells has not been analysed in detail. To investigate this, we generated a mouse model lacking ATG16L1 specifically in intestinal epithelial cells (Atg16l1△IEC) making these cells impaired in autophagy. Using a 3D small intestinal organoid culture model, which we enriched for Paneth cells and compared the proteomic profiles of organoids derived from the wild-type (WT) and the Atg16l1△IEC mice. We used an integrated computational approach combining protein-protein interaction networks, list of proteins potentially targeted by autophagy and functional information on the proteins with altered protein levels to identify the mechanistic link between autophagy-impairment and disrupted cellular process. 198 (70%) of the 284 altered proteins were more abundant in autophagy-impaired organoids than WT organoids that could be due to a reduced protein turnover. Combining the proteomic dataset with the potential target proteins of selective autophagy proteins revealed that 116 (41%) of the differentially abundant proteins could rely on autophagy-mediated turnover. Taken together, our results suggest that proteins with increased levels in autophagy-impaired background require an autophagy-mediated turnover mechanism, and that their altered levels in CD could affect key cellular processes. Consequently, we pointed out the importance of autophagy in controlling the turnover of proteins relevant in key Paneth cell functions such as exocytosis, apoptosis and DNA damage repair. Our study unravels autophagy-dependent cellular processes of Paneth cells that not directly relies on the autophagy process, rather than a selective protein turnover mechanism. The identified proteins and processes open new avenues for targeted, cell type-specific therapeutic interventions in CD.

Dataset Information

Expression data from Paneth cells isolated from mice on calorie restricted or ad libitum diet

Publications

mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake.

Similar Datasets

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