Gli1 Cells Couple with Type H Vessels and Are Required for Type H Vessel Formation.

Mesenchymal stem/stromal cells (MSCs) reside in the perivascular niche and modulate tissue/organ homeostasis; however, little is known about whether and how their localization and function are linked. Particularly, whether specific MSC subsets couple with and regulate specialized vessel subtypes is unclear. Here, we show that Gli1 cells, which are a subpopulation of MSCs couple with and regulate a specialized form of vasculature. The specific capillaries, i.e., CD31EMCN type H vessels, are the preferable vascular subtype which Gli1 cells are adjacent to in bone. Gli1 cells are further identified to be phenotypically coupled with type H endothelium during bone growth and defect healing. Importantly, Gli1 cell ablation inhibits type H vessel formation associated with suppressed bone generation and regeneration. Mechanistically, Gli1 cells initiate angiogenesis through Gli and HIF-1α signaling. These findings suggest a morphological and functional framework of Gli1 cells modulating coupled type H vasculature for tissue homeostasis and regenerative repair.