Heparan sulfate regulates myofibroblast heterogeneity and function to mediate niche homeostasis during alveolar morphogenesis.

ABSTRACT: Postnatal respiration requires bulk formation of alveoli that produces extensive surface area for gas diffusion from epithelium to the circulatory system. Alveolar morphogenesis initiates at late gestation or postnatal stage during mammalian development and is mediated by coordination among multiple cell types. Here we show that fibroblast-derived Heparan Sulfate Glycosaminoglycan (HS-GAG) is essential for maintaining a niche that supports alveolar formation by modulating both biophysical and biochemical cues. Gli1-CreER mediated deletion of HS synthase gene Ext1 in lung fibroblasts results in enlarged and simplified alveolar structures. Ablation of HS results in loss of a subset of PDGFRα^hi αSMA⁺ alveolar myofibroblasts residing in the distal alveolar region, which e

SUBMITTER: He H 

PROVIDER: S-EPMC11842828 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature