Mesenchymal stem cells (MSCs) reside in niches to maintain tissue homeostasis and contribute to repair and regeneration. Although the physiological functions of blood and lymphatic vasculature are well studied, their regulation of MSCs as niche components remains largely unknown. Using adult mouse incisors as a model, we uncover the role of Trp53 in regulating vascular composition through THBS2 to maintain mesenchymal tissue homeostasis. Loss of Trp53 in GLI1+ progeny increases arteries and decreases other vessel types. Platelet-derived growth factors from arteries deposit in the MSC region and interact with PDGFRA and PDGFRB. Significantly, PDGFRA+ and PDGFRB+ cells differentially contribute to defined cell lineages in the adult mouse incisor. Collectively, our results highlight Trp53’s importance in regulating the vascular niche for MSCs. They also shed light on how different arterial cells provide unique cues to regulate MSC subpopulations and maintain their heterogeneity. Furthermore, they provide mechanistic insight into MSC-vasculature crosstalk.

间充质干细胞 (MSC) 存在于微环境中，维持组织稳态并有助于修复和再生。尽管血液和淋巴管系统的生理功能已得到充分研究，但它们作为利基成分对 MSC 的调节仍知之甚少。使用成年小鼠门牙作为模型，我们揭示了Trp53在通过 THBS2 调节血管组成以维持间充质组织稳态中的作用。GLI1+ 后代中Trp53的缺失会增加动脉血管数量并减少其他血管类型。来自动脉的血小板衍生生长因子沉积在 MSC 区域并与 PDGFRA 和 PDGFRB 相互作用。值得注意的是，PDGFRA+ 和 PDGFRB+ 细胞对成年小鼠门牙中确定的细胞谱系的贡献不同。总的来说，我们的结果强调了Trp53在调节 MSC 血管生态位中的重要性。他们还揭示了不同的动脉细胞如何提供独特的信号来调节 MSC 亚群并维持其异质性。此外，它们还提供了对 MSC 脉管系统串扰的机制洞察。