Specialized pericyte subtypes in the pulmonary capillaries

Pericytes (PCs) are essential for capillary stability and homeostasis, with impaired PC function linked to diseases like pulmonary arterial hypertension (PAH). Investigating PC biology has been challenging due to the lack of specific markers, making it difficult to distinguish PCs from other stromal cells. Using bioinformatic analysis and RNAscope, we identified Higd1b as a unique gene marker for PCs and generated a novel knockin mouse line, Higd1b-CreERT2, that accurately labels PCs in the lung and heart. Single-cell RNA sequencing revealed two distinct Higd1b+ PC subtypes, with Type 1 PCs supporting capillary homeostasis and Type 2 PCs accumulating in arterioles, coexpressing smooth muscle markers and increased levels of Vimentin under hypoxic conditions. Lastly, healthy human lung PCs with upregulation of Vimentin exhibited increased adhesion, migration, and increased expression levels of SM22 in vitro. These findings highlight the specialization of pulmonary PCs and their contribution to vascular remodeling in hypoxia-induced pulmonary hypertension (PH), offering new insights into PC function and regulation.