Using single-cell RNA sequencing (scRNAseq), we identified novel molecular and cellular mechanisms underlying the lung abnormalities observed in our <i>Col1a1</i> <sup><i>Aga2/+</i></sup> (<i>Aga2</i>) mouse, which recapitulates a moderate form of OI. Here, COL1A1 is linked to osteogenesis imperfecta.