Fishman V S, Shnayder T A, Orishchenko K E, Bader M, Alenina N, Serov O L
a Institute of Cytology and Genetics ; Novosibirsk , Russia.
Cell Cycle. 2015;14(8):1188-96. doi: 10.1080/15384101.2015.1012875.
Direct lineage conversion is a promising approach for disease modeling and regenerative medicine. Cell divisions play a key role in reprogramming of somatic cells to pluripotency, however their role in direct lineage conversion is not clear. Here we used transdifferentiation of fibroblasts into neuronal cells by forced expression of defined transcription factors as a model system to study the role of cellular division in the direct conversion process. We have shown that conversion occurs in the presence of the cell cycle inhibitors aphidicolin or mimosine. Moreover, overexpression of the cell cycle activator cMyc negatively influences the process of direct conversion. Overall, our results suggest that cell divisions are not essential for the direct conversion of fibroblasts into neuronal cells.
直接谱系转化是疾病建模和再生医学中一种很有前景的方法。细胞分裂在将体细胞重编程为多能性过程中起着关键作用,然而其在直接谱系转化中的作用尚不清楚。在这里,我们通过强制表达特定转录因子将成纤维细胞转分化为神经元细胞作为模型系统,来研究细胞分裂在直接转化过程中的作用。我们已经表明,在细胞周期抑制剂阿非迪霉素或含羞草碱存在的情况下转化仍会发生。此外,细胞周期激活剂cMyc的过表达对直接转化过程产生负面影响。总体而言,我们的结果表明细胞分裂对于成纤维细胞直接转化为神经元细胞并非必不可少。