Robust and Reproducible Generation of Induced Neural Stem Cells from Human Somatic Cells by Defined Factors

通过特定因素从人类体细胞稳健且可重复地生成诱导神经干细胞

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作者:Tae Hwan Kwak, Sai Hali, Sungmin Kim, Jonghun Kim, Hyeonwoo La, Kee-Pyo Kim, Kwon Ho Hong, Chan Young Shin, Nam-Hyung Kim, Dong Wook Han

Conclusions

Our factor combination could robustly and reproducibly generate hiNSCs from human somatic cells with distinct origins. Therefore, our novel reprogramming strategy might serve as a useful tool for hiNSC-based clinical application.

Methods

We introduced distinct factor combinations, OSKM (OCT4+SOX2+KLF4+C-MYC), OCT4 alone, SOX2 alone, SOX2+HMGA2, BRN4+SKM+SV40LT (BSKMLT), SKLT, SMLT, and SKMLT and performed comparative analysis of reprogramming potentials of distinct factor combinations in hiNSC generation.

Results

Here we show that ectopic expression of five reprogramming factors, BSKMLT leads the robust hiNSC generation (>80 folds enhanced efficiency) from human somatic cells compared with previously described factor combinations. With our combination, we were able to observe hiNSC conversion within 7 days of transduction. Throughout further optimization steps, we found that both BRN4 and KLF4 are not essential for hiNSC conversion. Conclusions: Our factor combination could robustly and reproducibly generate hiNSCs from human somatic cells with distinct origins. Therefore, our novel reprogramming strategy might serve as a useful tool for hiNSC-based clinical application.

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