D2.439 - Corticosteroids promoted organoid formation and differentiation of SSEA-1+ lung stem/progenitor cells

Lung immaturity is a major cause of mortality in preterm infants, often leading to respiratory distress syndrome (RDS). Antenatal corticosteroid has been used as a standard treatment for women facing the risk of premature delivery, but their mechanisms, especially on lung stem cells, remain unclear. This study aimed to investigate the effects of corticosteroid on pulmonary SSEA-1⁺ stem/progenitor cells and derived lung organoids. 

We isolated pulmonary SSEA-1⁺ stem/progenitor cells from fetal lungs and established an organoid culture system to assess their biomarker expression and gene profiles. In addition, we performed in vivo experiments by administering dexamethasone to pregnant mice, followed by comparison of gene expression and morphological changes in fetal lungs with those of the control group.

Our results indicated that sustained dexamethasone treatment upregulated club cell marker Scgb1a1 and CCSP secretion, while downregulating ciliated (Foxj1) and goblet (Muc5ac) cell markers, with loss of ciliated cells in organoids as revealed by immunofluorescence staining. It also increased type I and type II alveolar cell markers at both mRNA and protein levels, while suppressing Sox2 and Sox9, transcription factors typically expressed in airway and alveolar progenitor cells, respectively. In vivo results also reflected the in vitro findings with reduction of SSEA-1⁺ cells and increase of basal and AT2 markers via Sox2/Sox9 inhibition.

These results demonstrated that dexamethasone drives SSEA-1⁺ stem cells toward alveolar differentiation, forming alveolar-like organoids and accelerating maturation. These findings highlight corticosteroids' benefits for lung development