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  FGF10 Triggers de novo Alveologenesis in a Bronchopulmonary Dysplasia Model: Impact on Resident Mesenchymal Niche Cells

Taghizadeh, S., Chao, C.-M., Guenther, S., Glaser, L., Gersmann, L., Michel, G., et al. (2022). FGF10 Triggers de novo Alveologenesis in a Bronchopulmonary Dysplasia Model: Impact on Resident Mesenchymal Niche Cells. STEM CELLS. doi:10.1093/stmcls/sxac025.

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Taghizadeh, Sara, Author
Chao, Cho-Ming, Author
Guenther, Stefan1, Author              
Glaser, Lea, Author
Gersmann, Luisa, Author
Michel, Gabriela, Author
Kraut, Simone, Author
Goth, Kerstin, Author
Koepke, Janine, Author
Heiner, Monika, Author
Vazquez-Armendariz, Ana Ivonne, Author
Herold, Susanne2, Author              
Samakovlis, Christos2, Author              
Weissmann, Norbert, Author
Ricci, Francesca, Author
Aquila, Giorgio, Author
Boyer, Laurent, Author
Ehrhardt, Harald, Author
Minoo, Parviz, Author
Bellusci, Saverio, Author
Rivetti, Stefano, Author more..
Affiliations:
1Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591695              
2Lung Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591698              

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 Abstract: Bronchopulmonary dysplasia (BPD) is a neonatal lung disease developing in premature babies characterized by arrested alveologenesis and associated with decreased Fibroblast growth factor 10 (FGF10) expression. One-week hyperoxia (HYX) exposure of newborn mice leads to a permanent arrest in alveologenesis. To test the role of Fgf10 signaling to promote de novo alveologenesis following hyperoxia, we used transgenic mice allowing inducible expression of Fgf10 and recombinant FGF10 (rFGF10) protein delivered intraperitoneally. We carried out morphometry analysis, and IF on day 45. Alveolospheres assays were performed co-culturing AT2s from normoxia (NOX) with FACS-isolated Sca1(Pos) resident mesenchymal cells (rMC) from animals exposed to NOX, HYX-PBS, or HYX-FGF10. scRNAseq between rMC-Sca1(Pos) isolated from NOX and HYX-PBS was also carried out. Transgenic overexpression of Fgf10 and rFGF10 administration rescued the alveologenesis defects following HYX. Alveolosphere assays indicate that the activity of rMC-Sca1(Pos) is negatively impacted by HYX and partially rescued by rFGF10 treatment. Analysis by IF demonstrates a significant impact of rFGF10 on the activity of resident mesenchymal cells. scRNAseq results identified clusters expressing Fgf10, Fgf7, Pdgfra, and Axin2, which could represent the rMC niche cells for the AT2 stem cells. In conclusion, we demonstrate that rFGF10 administration is able to induce de novo alveologenesis in a BPD mouse model and identified subpopulations of rMC-Sca1(Pos) niche cells potentially representing its cellular target.

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 Dates: 2022-04-12
 Publication Status: Published online
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 Identifiers: ISI: 000796690700001
DOI: 10.1093/stmcls/sxac025
PMID: 35437594
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Title: STEM CELLS
Source Genre: Journal
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Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 1066-5099