Retrospective analysis reveals the early origin and development of pulmonary perivascular cells [MeD-seq]

Emerging evidence suggests that pericytes play a significant role in various lung diseases, such as congenital diaphragmatic hernia and chronic obstructive pulmonary disease. However, characterizing pericytes remains challenging, impeding our understanding of their exact role in lung development and disease.

Therefore, we used a novel cell tracing technology based on a bacterial DNA cytosine methyltransferase (Dcm) fused to RNA polymerase II (DCM-TM) to methylate active genes. The doxycycline inducible Dcm-PolII fusion protein was activated at specific time points during gestation, while the epigenetically labeled genes were analyzed at later time points. This retrospective cell tracing was coupled to single-cell RNA sequencing to track the development of mouse pulmonary pericytes at the single cell level.