Hu E, Tontonoz P, Spiegelman B M
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9856-60. doi: 10.1073/pnas.92.21.9856.
Skeletal muscle and adipose tissue development often has a reciprocal relationship in vivo, particularly in myodystrophic states. We have investigated whether determined myoblasts with no inherent adipogenic potential can be induced to transdifferentiate into mature adipocytes by the ectopic expression of two adipogenic transcription factors, PPAR gamma and C/EBP alpha. When cultured under optimal conditions for muscle differentiation, murine G8 myoblasts expressing PPAR gamma and C/EBP alpha show markedly reduced levels of the myogenic basic helix-loop-helix proteins MyoD, myogenin, MRF4, and myf5 and are completely unable to differentiate into myotubes. Under conditions permissive for adipogenesis including a PPAR activator, these cells differentiate into mature adipocytes that express molecular markers characteristic of this lineage. Our results demonstrate that a developmental switch between these two related but highly specialized cell types can be controlled by the expression of key adipogenic transcription factors. These factors have an ability to inhibit myogenesis that is temporally and functionally separate from their ability to stimulate adipogenesis.
在体内，骨骼肌和脂肪组织的发育通常存在相互关系，尤其是在肌营养不良状态下。我们研究了没有内在成脂潜能的特定成肌细胞是否能通过两种成脂转录因子PPARγ和C/EBPα的异位表达被诱导转分化为成熟脂肪细胞。当在肌肉分化的最佳条件下培养时，表达PPARγ和C/EBPα的小鼠G8成肌细胞显示出肌源性碱性螺旋-环-螺旋蛋白MyoD、肌细胞生成素、MRF4和myf5的水平显著降低，并且完全无法分化为肌管。在允许脂肪生成的条件下，包括PPAR激活剂，这些细胞分化为表达该谱系特征性分子标记的成熟脂肪细胞。我们的结果表明，这两种相关但高度特化的细胞类型之间的发育转换可以通过关键成脂转录因子的表达来控制。这些因子具有抑制肌生成的能力，这在时间和功能上与其刺激脂肪生成的能力是分开的。
