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Niches of Wnt/Beta-Catenin Signaling in Distal Adult Human and Mouse Lung During Homeostasis and Injury
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A2896 - Niches of Wnt/Beta-Catenin Signaling in Distal Adult Human and Mouse Lung During Homeostasis and Injury
Author Block: A. Lam, A. Misharin, A. Flozak, C. Chung, G. Budinger, C. J. Gottardi; Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL, United States.
Background: Wnt/beta-catenin signaling is critical in normal lung development. In the adult lung, the cell contextual activity of the Wnt/beta-catenin pathway is poorly understood during both homeostasis and disease. We hypothesize that an organization of Wnt-secretor and Wnt-responder cells exists in the distal lung that is critical to the maintenance of the lung parenchyma and is aberrant in the development of fibrosis. Methods: Using RNA-seq analysis of primary human and mouse lung cells and RNAscope in situ hybridization of paraffin-embedded sections of mouse and human lungs, we determined the detailed expression of Wnt/beta-catenin pathway genes and their spatial localization. Results/Conclusions: We found that Wnt-expressing and Wnt-responding cells appear distinct. Wnt-responding cells were defined by the expression of the universal Wnt/beta-catenin target gene AXIN2, as well as NKD1, RNF43 or ZNF3 target genes. Cells largely expressed one flavor of Wnt ligand. R-spondins, which are structurally disctinct from Wnts but work synergistically with Wnts to sustain Wnt/beta-catenin signaling, and their receptors are expressed in different cell type than Wnts. These findings support the emerging concept that Wnt-expressor and Wnt-responder cells are non-overlapping and drive tissue organization through defined epithelial/mesenchymal niches.
Author Block: A. Lam, A. Misharin, A. Flozak, C. Chung, G. Budinger, C. J. Gottardi; Pulmonary and Critical Care Medicine, Northwestern University, Chicago, IL, United States.
Background: Wnt/beta-catenin signaling is critical in normal lung development. In the adult lung, the cell contextual activity of the Wnt/beta-catenin pathway is poorly understood during both homeostasis and disease. We hypothesize that an organization of Wnt-secretor and Wnt-responder cells exists in the distal lung that is critical to the maintenance of the lung parenchyma and is aberrant in the development of fibrosis. Methods: Using RNA-seq analysis of primary human and mouse lung cells and RNAscope in situ hybridization of paraffin-embedded sections of mouse and human lungs, we determined the detailed expression of Wnt/beta-catenin pathway genes and their spatial localization. Results/Conclusions: We found that Wnt-expressing and Wnt-responding cells appear distinct. Wnt-responding cells were defined by the expression of the universal Wnt/beta-catenin target gene AXIN2, as well as NKD1, RNF43 or ZNF3 target genes. Cells largely expressed one flavor of Wnt ligand. R-spondins, which are structurally disctinct from Wnts but work synergistically with Wnts to sustain Wnt/beta-catenin signaling, and their receptors are expressed in different cell type than Wnts. These findings support the emerging concept that Wnt-expressor and Wnt-responder cells are non-overlapping and drive tissue organization through defined epithelial/mesenchymal niches.
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