Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors
Direct Reprogramming of Fibroblasts into Neural Stem Cells by Defined Factors
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DOI：
10.1016/j.stem.2012.02.021
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发表时间：
2012-04-06
期刊：
影响因子：
23.9
通讯作者：
Schoeler, Hans R.
中科院分区：
文献类型：
--
作者：
Han, Dong Wook;Tapia, Natalia;Schoeler, Hans R.
最近的研究表明，定义的转录因子组可以直接将分化的体细胞重新编程为不同的分化细胞类型，而无需经过多能状态，但所得细胞的有限增殖和谱系潜力限制了其潜在应用的范围。在这里，我们表明，转录因子（Brn 4/Pou 3f 4，Sox 2，Klf 4，c-Myc，加上E47/Tcf 3）的组合诱导小鼠成纤维细胞直接获得神经干细胞的身份，我们称之为诱导神经干细胞（iNSC）。将成纤维细胞直接重编程为iNSC是一个渐进的过程，其中供体转录程序随时间沉默。iNSC表现出与野生型NSC相似细胞形态、基因表达、表观遗传特征、分化潜能和自我更新能力以及体外和体内功能。我们的结论是，分化的细胞可以直接重编程成特定的体干细胞类型的特定转录因子的定义集。
Recent studies have shown that defined sets of transcription factors can directly reprogram differentiated somatic cells to a different differentiated cell type without passing through a pluripotent state, but the restricted proliferative and lineage potential of the resulting cells limits the scope of their potential applications. Here we show that a combination of transcription factors (Brn4/Pou3f4, Sox2, Klf4, c-Myc, plus E47/Tcf3) induces mouse fibroblasts to directly acquire a neural stem cell identity which we term as induced neural stem cells (iNSCs). Direct reprogramming of fibroblasts into iNSCs is a gradual process in which the donor transcriptional program is silenced over time. iNSCs exhibit cell morphology, gene expression, epigenetic features, differentiation potential, and self-renewing capacity, as well as in vitro and in vivo functionality similar to those of wild-type NSCs. We conclude that differentiated cells can be reprogrammed directly into specific somatic stem cell types by defined sets of specific transcription factors.