Notch signaling in the dynamics of perivascular stem cells and their niches

The Notch signaling pathway is a fundamental regulator of cell fate determination in homeostasis and regeneration. In this work, we aimed to determine how Notch signaling mediates the interactions between perivascular stem cells and their niches in human dental mesenchymal tissues, both in homeostatic and regenerative conditions. By single cell RNA sequencing analysis, we showed that perivascular cells across the dental pulp and periodontal human tissues all express NOTCH3, and that these cells are important for the response to traumatic injuries in vivo in a transgenic mouse model. We further showed that the behavior of perivascular NOTCH3‐expressing stem cells could be modulated by cellular and molecular cues deriving from their microenvironments. Taken together, the present studies, reinforced by single‐cell analysis, reveal the pivotal importance of Notch signaling in the crosstalk between perivascular stem cells and their niches in tissue homeostasis and regeneration. In the dental pulp and the periodontium, mesenchymal stem cells (MSCs) are highly similar, are mostly located around blood vessels, and express NOTCH3. These NOTCH3+ MSCs are important for the reaction of dental tissues to injury. In both tissues, endothelial cells adjacent to NOTCH3+ MSCs express NOTCH ligands, which could thus mediate the molecular crosstalk between MSCs and their perivascular niche.