Details

Autor(en) / Beteiligte

• Conroy, Lindsey R
• Clarke, Harrison A
• Allison, Derek B
• Valenca, Samuel Santos
• Sun, Qi
• Hawkinson, Tara R
• Young, Lyndsay E A
• Ferreira, Juanita E
• Hammonds, Autumn V
• Dunne, Jaclyn B
• McDonald, Robert J
• Absher, Kimberly J
• Dong, Brittany E
• Bruntz, Ronald C
• Markussen, Kia H
• Juras, Jelena A
• Alilain, Warren J
• Liu, Jinze
• Gentry, Matthew S
• Angel, Peggi M
• Waters, Christopher M
• Sun, Ramon C

Titel

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis

Ist Teil von

• Nature communications, 2023-05, Vol.14 (1), p.2759-2759, Article 2759

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed blunted N-linked glycan levels and nearly 90% reduction in endpoint fibrosis when compared to WT animals. Collectively, we provide conclusive evidence that lysosomal utilization of glycogen is required for pulmonary fibrosis progression. In summary, our study provides a roadmap to leverage spatial metabolomics to understand foundational biology in pulmonary diseases.