PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis
PDGFRα controls the balance of stromal and adipogenic cells during adipose tissue organogenesis
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DOI：
10.1242/dev.135962
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发表时间：
2017-01-01
期刊：
影响因子：
4.6
通讯作者：
Olson, Lorin E.
中科院分区：
文献类型：
--
作者：
Sun, Chengyi;Berry, William L.;Olson, Lorin E.
脂肪组织分布在全身各处的储存库中，在能量储存和产热方面起着特殊的作用。PDGFRα是脂肪细胞前体的标志物，PDGFRA活性增加会导致成年小鼠脂肪组织纤维化。然而，PDGFRA在脂肪组织器官发生中的作用尚不清楚。在这里，通过分析具有增加PDGFRA活性的膜旁或激酶域点突变的小鼠(V561D或D842V)，我们发现PDGFRA的激活以组织自主的方式抑制胚胎白色脂肪组织的器官形成。通过谱系追踪分析，我们还发现，表达胶原的前体成纤维细胞在胚胎中分化为白色脂肪细胞。PDGFRA抑制这些前体细胞的脂肪细胞形成，而促进间质成纤维细胞的形成。脂肪细胞和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。PDGFRA的激活也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和成脂细胞扩张的重要性，PDGFRA的活动协调了胚胎中这一关键过程。
Adipose tissue is distributed in depots throughout the body with specialized roles in energy storage and thermogenesis. PDGFR alpha is a marker of adipocyte precursors, and increased PDGFRa activity causes adipose tissue fibrosis in adult mice. However, the function of PDGFRa during adipose tissue organogenesis is unknown. Here, by analyzing mice with juxtamembrane or kinase domain point mutations that increase PDGFRa activity (V561D or D842V), we found that PDGFRa 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. PDGFRa 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. PDGFRa 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 PDGFRa activity coordinating this crucial process in the embryo.