Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
Science. 2011 Jan 21;331(6015):304-8. doi: 10.1126/science.1199082. Epub 2010 Dec 9.
The ability of transcription factors to directly reprogram the identity of cell types is usually restricted and is defined by cellular context. Through the ectopic expression of single Caenorhabditis elegans transcription factors, we found that the identity of mitotic germ cells can be directly converted into that of specific neuron types: glutamatergic, cholinergic, or GABAergic. This reprogramming event requires the removal of the histone chaperone LIN-53 (RbAp46/48 in humans), a component of several histone remodeling and modifying complexes, and this removal can be mimicked by chemical inhibition of histone deacetylases. Our findings illustrate the ability of germ cells to be directly converted into individual, terminally differentiated neuron types and demonstrate that a specific chromatin factor provides a barrier for cellular reprogramming.
转录因子直接重编程细胞类型的能力通常受到限制，并由细胞环境定义。通过异位表达单个秀丽隐杆线虫转录因子，我们发现有丝分裂生殖细胞的身份可以直接转化为特定神经元类型：谷氨酸能、胆碱能或 GABA 能。这种重编程事件需要去除组蛋白伴侣 LIN-53（人类的 RbAp46/48），它是几种组蛋白重塑和修饰复合物的一个组成部分，这种去除可以通过化学抑制组蛋白去乙酰化酶来模拟。我们的研究结果说明了生殖细胞能够直接转化为单个终末分化的神经元类型，并表明特定的染色质因子为细胞重编程提供了障碍。
