Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Nat Commun. 2017 Jun 26;8:15926. doi: 10.1038/ncomms15926.
Adipose progenitor cells (APCs) reside in a vascular niche, located within the perivascular compartment of adipose tissue blood vessels. Yet, the signals and mechanisms that govern adipose vascular niche formation and APC niche interaction are unknown. Here we show that the assembly and maintenance of the adipose vascular niche is controlled by PPARγ acting within APCs. PPARγ triggers a molecular hierarchy that induces vascular sprouting, APC vessel niche affinity and APC vessel occupancy. Mechanistically, PPARγ transcriptionally activates PDGFRβ and VEGF. APC expression and activation of PDGFRβ promotes the recruitment and retention of APCs to the niche. Pharmacologically, targeting PDGFRβ disrupts APC niche contact thus blocking adipose tissue expansion. Moreover, enhanced APC expression of VEGF stimulates endothelial cell proliferation and expands the adipose niche. Consequently, APC niche communication and retention are boosted by VEGF thereby impairing adipogenesis. Our data indicate that APCs direct adipose tissue niche expansion via a PPARγ-initiated PDGFRβ and VEGF transcriptional axis.
脂肪祖细胞（APCs）位于血管壁龛中，位于脂肪组织血管的血管周腔室中。然而，调控脂肪血管壁龛形成和 APC 壁龛相互作用的信号和机制尚不清楚。在这里，我们发现 PPARγ 在 APC 中起作用，控制着脂肪血管壁龛的组装和维持。PPARγ 引发了一个分子层次结构，诱导血管发芽、APC 血管壁龛亲和性和 APC 血管占据。从机制上讲，PPARγ 转录激活 PDGFRβ 和 VEGF。APCs 表达和 PDGFRβ 的激活促进了 APC 向壁龛的募集和保留。通过药理学方法靶向 PDGFRβ 可破坏 APC 壁龛接触，从而阻止脂肪组织的扩张。此外，VEGF 增强 APC 的表达可刺激内皮细胞增殖并扩大脂肪壁龛。因此，VEGF 促进了 APC 壁龛通讯和保留，从而损害了脂肪生成。我们的数据表明，APCs 通过由 PPARγ 引发的 PDGFRβ 和 VEGF 转录轴来指导脂肪组织壁龛的扩张。
