Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nat Cell Biol. 2012 Jan 15;14(2):209-19. doi: 10.1038/ncb2411.
The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%-90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.
人多能干细胞的效用取决于有效的分化方案，这些方案可以将这些细胞转化为相关的成体细胞类型。在这里，我们报告了人多能干细胞向白色或棕色脂肪细胞的稳健和高效分化。我们发现，诱导性表达 PPARG2 单独或与 CEBPB 和/或 PRDM16 一起在多能干细胞衍生的间充质祖细胞中表达，可将其发育编程为白色或棕色脂肪细胞命运，效率为 85%-90%。这些脂肪细胞在不依赖转基因表达的情况下保持其特性，可以在培养中维持数周，表达成熟的标志物，并具有成熟的功能特性，如脂质分解和胰岛素反应性。当被移植到小鼠中时，编程细胞产生了具有白色或棕色脂肪组织的形态和功能特征的异位脂肪垫。这些结果表明，这些细胞可用于忠实地模拟人类疾病。
