Bracha Abigail L, Ramanathan Arvind, Huang Sui, Ingber Donald E, Schreiber Stuart L
[1] Vascular Biology Program, Department of Pathology and Department of Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] These authors contributed equally to this work.
Nat Chem Biol. 2010 Mar;6(3):202-204. doi: 10.1038/nchembio.301. Epub 2010 Jan 17.
The role of nutrients and metabolism in cellular differentiation is poorly understood. Using RNAi screening, metabolic profiling and small-molecule probes, we discovered that the knockdown of three metabolic enzymes-phosphoglycerate kinase (Pgk1), hexose-6-phosphate dehydrogenase (H6pd) and ATP citrate lyase (Acl)-induces differentiation of mouse C2C12 myoblasts even in the presence of mitogens. These enzymes and the pathways they regulate provide new targets for the control of myogenic differentiation in myoblasts and rhabdomyosarcoma cells.
营养素和代谢在细胞分化中的作用尚不清楚。通过RNA干扰筛选、代谢谱分析和小分子探针，我们发现敲低三种代谢酶——磷酸甘油酸激酶（Pgk1）、6-磷酸己糖脱氢酶（H6pd）和ATP柠檬酸裂解酶（Acl）——即使在有丝分裂原存在的情况下也能诱导小鼠C2C12成肌细胞分化。这些酶及其调节的途径为控制成肌细胞和横纹肌肉瘤细胞中的肌源性分化提供了新的靶点。
