Dataset Information

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): Bruker Daltonics solarix series

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

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Dataset's files

Source:

			Action	DRS
	20190701_Telocytes_02_NEDC_ATG_KO_Day1_PDGFRa_BW.tiff	Other
	20190701_Telocytes_02_NEDC_ATG_KO_Day2_PDGFRa_BW.tiff	Other
	20190701_Telocytes_02_NEDC_WT_Day1_PDGFRa_BW.tiff	Other
	20190701_Telocytes_02_NEDC_WT_Day2_PDGFRa_BW.tiff	Other
	Day_1_20190702_Telocytes_02_NEDC_20um_A.ibd	Other

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Publications

Autophagy in PDGFRα+ mesenchymal cells is essential for intestinal stem cell survival.

Yang Yang Y Gomez Maria M Marsh Timothy T Poillet-Perez Laura L Sawant Akshada A Chen Lei L Park Noel R NR Jackson S RaElle SR Hu Zhixian Z Alon Noa N Liu Chen C Debnath Jayanta J Guan Jun-Lin JL Davidson Shawn S Verzi Michael M White Eileen E

Proceedings of the National Academy of Sciences of the United States of America 20220510 21

Autophagy defects are a risk factor for inflammatory bowel diseases (IBDs) through unknown mechanisms. Whole-body conditional deletion of autophagy-related gene (Atg) Atg7 in adult mice (Atg7Δ/Δ) causes tissue damage and death within 3 mo due to neurodegeneration without substantial effect on intestine. In contrast, we report here that whole-body conditional deletion of other essential Atg genes Atg5 or Fip200/Atg17 in adult mice (Atg5Δ/Δ or Fip200Δ/Δ) caused death within 5 d due to rapid autoph ...[more]

PMID: 35537042

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Project description:Highly specialized cells are fundamental for proper functioning of complex organs. Variations in cell-type specific gene expression and protein composition have been linked to a variety of diseases. Although single cell technologies have emerged as valuable tools to address this cellular heterogeneity, a majority of these workflows lack sufficient in situ resolution for functional classification of cells and are associated with extremely long analysis time, especially when it comes to in situ proteomics. In addition, lack of understanding of single cell dynamics within their native environment limits our ability to explore the altered physiology in disease development. This limitation is particularly relevant in the mammalian brain, where different cell types perform unique functions and exhibit varying sensitivities to insults. The hippocampus, a brain region crucial for learning and memory, is of particular interest due to its obvious involvement in various neurological disorders. Here, we present a combination of experimental and data integration approaches for investigation of cellular heterogeneity and functional disposition within the mouse brain hippocampus using MALDI Imaging mass spectrometry (MALDI-IMS) and shotgun proteomics (LC-MS/MS) coupled with laser-capture microdissection (LCM) along with spatial transcriptomics. Within the dentate gyrus granule cells we identified two proteomically distinct cellular subpopulations that are characterized by a substantial number of discriminative proteins. These cellular clusters contribute to the overall functionality of the dentate gyrus by regulating redox homeostasis, mitochondrial organization, RNA processing, and microtubule organization. Importantly, most of the identified proteins matched their transcripts, verifying the in situ protein identification and supporting their functional analyses. By combining high-throughput spatial proteomics with transcriptomics, our approach enables reliable near-single-cell scale identification of proteins and profiling of inter-cellular heterogeneity within similar cell-types in tissues. This methodology has the potential to be applied to different biological conditions and tissues, providing a deeper understanding of cellular subpopulations in situ.