Endocrinology Program, University of California, Berkeley, Berkeley, CA 94720, USA.
Department of Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell Rep. 2018 Oct 23;25(4):1002-1017.e4. doi: 10.1016/j.celrep.2018.09.086.
Adipocytes arise from the commitment and differentiation of adipose precursors in white adipose tissue (WAT). In studying adipogenesis, precursor markers, including Pref-1 and PDGFRα, are used to isolate precursors from stromal vascular fractions of WAT, but the relation among the markers is not known. Here, we used the Pref-1 promoter-rtTA system in mice for labeling Pref-1 cells and for inducible inactivation of the Pref-1 target Sox9. We show the requirement of Sox9 for the maintenance of Pref-1 proliferative, early precursors. Upon Sox9 inactivation, these Pref-1 cells become PDGFRα cells that express early adipogenic markers. Thus, we show that Pref-1 cells precede PDGFRα cells in the adipogenic pathway and that Sox9 inactivation is required for WAT growth and expansion. Furthermore, we show that in maintaining early adipose precursors, Sox9 activates Meis1, which prevents adipogenic differentiation. Our study also demonstrates the Pref-1 promoter-rtTA system for inducible gene inactivation in early adipose precursor populations.
脂肪细胞来源于白色脂肪组织（WAT）中脂肪前体的定向分化和分化。在研究脂肪生成时，使用前体标志物，包括 Pref-1 和 PDGFRα，从 WAT 的基质血管部分分离前体，但这些标志物之间的关系尚不清楚。在这里，我们使用 Pref-1 启动子-rtTA 系统在小鼠中标记 Pref-1 细胞，并诱导 Pref-1 靶标 Sox9 的失活。我们证明 Sox9 对于维持 Pref-1 增殖的、早期的前体是必需的。Sox9 失活后，这些 Pref-1 细胞成为表达早期脂肪生成标志物的 PDGFRα 细胞。因此，我们表明 Pref-1 细胞在前脂肪细胞途径中先于 PDGFRα 细胞，并且 Sox9 失活对于 WAT 的生长和扩张是必需的。此外，我们表明 Sox9 通过激活 Meis1 来维持早期脂肪前体细胞，从而阻止脂肪生成分化。我们的研究还证明了 Pref-1 启动子-rtTA 系统可用于诱导早期脂肪前体细胞群中的基因失活。
