Journal
CELL REPORTS
Volume 39, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110608
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Funding
- Hastings Foundation
- NIH [HL143059, HL144932, HL62569-10]
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During alveologenesis, PDGFRa(+) cells secrete trophic molecules to maintain the pAT2 cell population, while TGF beta signaling maintains the PDGFRa(+) cells. This mechanism is also observed in lungs of preterm infants with bronchopulmonary dysplasia, indicating its evolutionary conservation.
The lung alveolus is lined with alveolar type 1 (AT1) and type 2 (AT2) epithelial cells. During alveologenesis, increasing demand associated with expanding alveolar numbers is met by proliferating progenitor AT2s (pAT2). Little information exists regarding the identity of this population and their niche microenvironment. We show that during alveologenesis, Hedgehog-responsive PDGFRa(+) progenitors (also known as SCMFs) are a source of secreted trophic molecules that maintain a unique pAT2 population. SCMFs are in turn maintained by TGF beta signaling. Compound inactivation of Alk5 T beta R2 in SCMFs reduced their numbers and depleted the pAT2 pool without impacting differentiation of daughter cells. In lungs of preterm infants who died with bronchopulmonary dysplasia, PDGFRa is reduced and the number of proliferative AT2s is diminished, indicating that an evolutionarily conserved mechanism governs pAT2 behavior during alveologenesis. SCMFs are a transient cell population, active only during alveologenesis, making them a unique stage-specific niche mesodermal cell type in mammalian organs.
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