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

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

• Panza, P.
• Kim, H. T.
• Lautenschläger, T.
• Piesker, J.
• Günther, S.
• Alayoubi, Y.
• Cleaver, O.
• Looso, M.
• Stainier, D. Y. R.