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Transcriptional effect of SPARCL1 treatment on lung alveolar organoids

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 SPARCL1 as an extracellular matrix molecule that can promote AT2 cell differentiation in vitro. SPARCL1-treated organoids display lysozyme upregulation and a doubling in the number of differentiated AT2 cells at the expense of intermediate progenitors. SPARCL1 also induces the upregulation of NF-κB target genes, and suppression of NF-κB activation in lung organoids blocked SPARCL1 effects. NF-κB activation by 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE279892 | GEO | 2025/03/21

REPOSITORIES: GEO

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