Tang Qi-Qun, Otto Tamara C, Lane M Daniel
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9607-11. doi: 10.1073/pnas.0403100101. Epub 2004 Jun 21.
The increase of adipose tissue mass associated with obesity is due in part to an increase in the number of adipocytes. This hyperplasia results from recruitment of pluripotent stem cells present in the vascular stroma of adipose tissue. A model cell culture system has been developed that recapitulates this process both ex vivo and in vivo. After treatment of pluripotent C3H10T1/2 stem cells with bone morphogenic protein 4 (BMP4) during proliferation followed by differentiation inducers at growth arrest, the cells synchronously enter S phase and undergo mitotic clonal expansion, a hallmark of preadipocyte differentiation. Upon exiting the cell cycle, these cells express adipocyte markers and acquire adipocyte characteristics at high frequency. C3H10T1/2 cells treated with BMP4 in cell culture and implanted s.c. into athymic mice develop into tissue indistinguishable from adipose tissue in normal fat depots. We interpret the findings as evidence that BMP4 is capable of triggering commitment of pluripotent C3H10T1/2 stem cells to the adipocyte lineage.
与肥胖相关的脂肪组织量增加部分归因于脂肪细胞数量的增加。这种增生源于脂肪组织血管基质中存在的多能干细胞的募集。已经开发出一种模型细胞培养系统，该系统在体外和体内都能重现这一过程。在用骨形态发生蛋白4（BMP4）处理多能C3H10T1/2干细胞使其增殖，然后在生长停滞期用分化诱导剂处理后，这些细胞同步进入S期并经历有丝分裂克隆扩增，这是前脂肪细胞分化的一个标志。在退出细胞周期后，这些细胞高频表达脂肪细胞标志物并获得脂肪细胞特征。在细胞培养中用BMP4处理并皮下植入无胸腺小鼠的C3H10T1/2细胞发育成与正常脂肪库中的脂肪组织难以区分的组织。我们将这些发现解释为BMP4能够触发多能C3H10T1/2干细胞向脂肪细胞谱系定向分化的证据。
