The Cellular Origin of the Pulmonary Pericyte

Emerging evidence suggests pericytes play a significant role in various lung diseases. However, characterizing pericytes remains challenging, impeding our understanding of their role in lung development and disease. Using single-cell RNA sequencing and DCM-time machine technology, we tracked the development of mouse pulmonary pericytes. Our study revealed the differentiation of perivascular progenitors into pericytes and vascular smooth muscle cells. Temporal analysis uncovered dynamic gene expression profiles during pericyte differentiation, highlighting pathways crucial for pulmonary vascular development. Further analysis showed intricate signaling interactions between pericyte progenitors and mature pericytes, and we validated Mcam as a bona fide pulmonary pericyte marker. These findings challenge conventional views on pericyte origin and underscore the importance of accurate pericyte identification in developmental and disease contexts. Overall, this study enhances our understanding of pulmonary pericyte ontogeny and differentiation, offering insights into their potential as therapeutic targets in pericyte-associated lung diseases.