Hedgehog-responsive PDGFRa(+) fibroblasts maintain a unique pool of alveolar epithelial progenitor cells during alveologenesis

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 TGFβ signaling. Compound inactivation of Alk5 TβR2 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.

  • Gao, F.
  • Li, C.
  • Danopoulos, S.
  • Al Alam, D.
  • Peinado, N.
  • Webster, S.
  • Borok, Z.
  • Kohbodi, G. A.
  • Bellusci, S.
  • Minoo, P.

Keywords

  • Animals
  • Cell Differentiation/physiology
  • Epithelial Cells
  • Fibroblasts
  • *Hedgehogs
  • Humans
  • Infant, Newborn
  • *Infant, Premature
  • Lung
  • Organogenesis
  • Receptor Protein-Tyrosine Kinases/metabolism
  • Stem Cells/metabolism
  • Alveologenesis
  • Bpd
  • CP: Cell biology
  • CP: Developmental biology
  • Niche
  • Organoid
  • Tgfβ
  • mesenchyme
  • progenitor AT2
  • scRNAseq
  • stem cells
Publication details
DOI: 10.1016/j.celrep.2022.110608
Journal: Cell Rep
Pages: 110608
Number: 1
Work Type: Original
Access number: 35385750
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