Autophagy in PDGFRα+ Mesenchymal Cells is Essential for Intestinal Stem Cell Survival: MALDI data

ABSTRACT: Autophagy defects are a risk factor for Inflammatory Bowel Diseases (IBD) through unknown mechanisms. Whole-body conditional deletion of essential autophagy gene (ATG) Atg7 in adult mice (Atg7Δ/Δ) causes tissue damage and death within three months due to neurodegeneration without substantial effect on intestine. In contrast, we report here that whole-body conditional Atg5 deletion in adult mice (Atg5Δ/Δ) caused death within five days due to rapid autophagy inhibition, elimination of ileum stem cells, and loss of barrier function. Atg5Δ/Δ mice lost PDGFRα+ mesenchymal cells (PMCs) and Wnt signaling essential for stem cell renewal, which were partially rescued by exogenous Wnt. To assess the metabolic consequences of ATG5 loss in PMCs and the ileum, we performed Matrix-assisted laser desorption ionization (MALDI) coupled to imaging mass spectrometry (IMS) (MALDI-IMS) to distinguish between a specific metabolic defect in PMCs and an effect on the entire ileum.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Mesenchymal Cell, Small Intestine

DISEASE(S): Disease Free

SUBMITTER: Yang Yang  

LAB HEAD: Eileen White

PROVIDER: PXD023428 | Pride | 2022-05-26

REPOSITORIES: Pride