RT Journal Article
SR Electronic
T1 FGF10 triggers de novo alveologenesis in a BPD model: impact on the resident mesenchymal niche cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.03.14.484213
DO 10.1101/2022.03.14.484213
A1 Sara Taghizadeh
A1 Cho-Ming Chao
A1 Stefan Guenther
A1 Lea Glaser
A1 Luisa Gersmann
A1 Gabriela Michel
A1 Simone Kraut
A1 Kerstin Goth
A1 Janine Koepke
A1 Monika Heiner
A1 Ana Ivonne Vazquez-Armendariz
A1 Susanne Herold
A1 Christos Samakovolis
A1 Norbert Weissmann
A1 Francesca Ricci
A1 Giorgio Aquila
A1 Laurent Boyer
A1 Harald Ehrhardt
A1 Parviz Minoo
A1 Saverio Bellusci
A1 Stefano Rivetti
YR 2022
UL http://biorxiv.org/content/early/2022/03/16/2022.03.14.484213.abstract
AB 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 Sca1Pos resident mesenchymal cells (rMC) from animals exposed to NOX, HYX+PBS, or HYX+FGF10. scRNAseq between rMC-Sca1Pos isolated from NOX and HYX+PBS were also carried out. Transgenic overexpression of Fgf10 and rFGF10 administration rescued the alveologenesis defects following HYX. Alveolosphere assays indicate that the activity of rMC-Sca1Pos 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-Sca1Pos niche cells potentially representing its cellular target.Competing Interest StatementThe authors have declared no competing interest.