Work

The lung microvasculature promotes alveolar type 2 cell differentiation via secreted SPARCL1

Year: 2025

Type: article

Abstract: Lung endothelial cells (ECs) and pericytes are closely juxtaposed with the respiratory epithelium before birth and thus may have instructive roles during development. To test this hypothesis, we screened EC-secreted proteins for their ability to alter cell differentiation in alveolar organoids. We identified secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) as an extracellular matrix molecule that can promote alveolar type 2 (AT2) cell differentiation in vitro. SPARCL1-treated organoids display lysozyme upregulation and a doubling in the number of AT2 cells at the expense of intermediate progenitors. SPARCL1 also induces the upregulation of nuclear factor κB (NF-κB) target genes, and suppression of NF-κB activation in lung organoids blocked SPARCL1 effects. NF-κB activation by lipopolysaccharide (LPS) was sufficient to induce AT2 cell differentiation; however, pharmacological inhibition of the pathway alone did not prevent it. These data support a role for SPARCL1 and NF-κB in alveolar cell differentiation and suggest a potential value in targeting this signaling axis to promote alveolar maturation and regeneration.

Source: Stem Cell Reports

DOI: 10.1016/j.stemcr.2025.102451