The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
The Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Stem Cell Reports. 2014 Dec 9;3(6):948-56. doi: 10.1016/j.stemcr.2014.10.001. Epub 2014 Nov 6.
Overexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors.
转录因子的过表达已被用于直接将体细胞重编程为多种其他分化细胞类型，包括多能神经干细胞（NSC），可用于生成神经元和神经胶质细胞。然而，在不依赖诱导因子的情况下维持 NSC 状态的能力以及体细胞供体细胞的身份仍然是转分化中两个未解决的重要问题。在这里，我们使用四环素诱导型转录因子的转导来产生稳定的三潜能 NSC。诱导的 NSC（iNSC）在没有外源因子表达的情况下保持其特性，并且在转录、表观遗传和功能上与原代脑源性 NSC 相似。重要的是，我们还从多种成年细胞类型，包括成熟的肝和 B 细胞中生成了三潜能 iNSC。我们的结果表明，通过表达特定组合的转录因子，可以从非外胚层细胞诱导出自我维持增殖的神经细胞。
