Sun Chengyi, Berry William L, Olson Lorin E
Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Development. 2017 Jan 1;144(1):83-94. doi: 10.1242/dev.135962.
Adipose tissue is distributed in depots throughout the body with specialized roles in energy storage and thermogenesis. PDGFRα is a marker of adipocyte precursors, and increased PDGFRα activity causes adipose tissue fibrosis in adult mice. However, the function of PDGFRα during adipose tissue organogenesis is unknown. Here, by analyzing mice with juxtamembrane or kinase domain point mutations that increase PDGFRα activity (V561D or D842V), we found that PDGFRα activation inhibits embryonic white adipose tissue organogenesis in a tissue-autonomous manner. By lineage tracing analysis, we also found that collagen-expressing precursor fibroblasts differentiate into white adipocytes in the embryo. PDGFRα inhibited the formation of adipocytes from these precursors while favoring the formation of stromal fibroblasts. This imbalance between adipocytes and stromal cells was accompanied by overexpression of the cell fate regulator Zfp521. PDGFRα activation also inhibited the formation of juvenile beige adipocytes in the inguinal fat pad. Our data highlight the importance of balancing stromal versus adipogenic cell expansion during white adipose tissue development, with PDGFRα activity coordinating this crucial process in the embryo.
脂肪组织分布于全身各储存部位，在能量储存和产热方面发挥着特殊作用。血小板衍生生长因子受体α（PDGFRα）是脂肪细胞前体的标志物，PDGFRα活性增加会导致成年小鼠脂肪组织纤维化。然而，PDGFRα在脂肪组织器官发生过程中的功能尚不清楚。在此，通过分析具有增加PDGFRα活性的近膜或激酶结构域点突变（V561D或D842V）的小鼠，我们发现PDGFRα激活以组织自主方式抑制胚胎白色脂肪组织器官发生。通过谱系追踪分析，我们还发现表达胶原蛋白的前体成纤维细胞在胚胎中分化为白色脂肪细胞。PDGFRα抑制这些前体形成脂肪细胞，同时促进基质成纤维细胞的形成。脂肪细胞与基质细胞之间的这种失衡伴随着细胞命运调节因子Zfp521的过度表达。PDGFRα激活还抑制腹股沟脂肪垫中幼年米色脂肪细胞的形成。我们的数据强调了在白色脂肪组织发育过程中平衡基质细胞与脂肪生成细胞扩张的重要性，PDGFRα活性在胚胎中协调这一关键过程。
