Amenable epigenetic traits of dental pulp stem cells underlie high capability of xeno-free episomal reprogramming

牙髓干细胞的适宜表观遗传特性是无异种基因组重编程高能力的基础

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作者:Srijaya Thekkeparambil Chandrabose, Sandhya Sriram, Subha Subramanian, Shanshan Cheng, Wee Kiat Ong, Steve Rozen, Noor Hayaty Abu Kasim, Shigeki Sugii

Background

While a shift towards non-viral and animal component-free

Conclusion

In conclusion, our study provides underlying epigenetic mechanisms that establish a robust platform for efficient generation of iPS cells from DPSCs, facilitating industrial and clinical use of iPS technology for therapeutic needs.

Methods

Here, we show a robust episomal and xeno-free reprogramming strategy for human iPS generation from dental pulp stem cells (DPSCs) which renders good efficiency (0.19%) over a short time frame (13-18 days).

Results

The robustness of DPSCs as starting cells for iPS induction is found due to their exceptional inherent stemness properties, developmental origin from neural crest cells, specification for tissue commitment, and differentiation capability. To investigate the epigenetic basis for the high reprogramming efficiency of DPSCs, we performed genome-wide DNA methylation analysis and found that the epigenetic signature of DPSCs associated with pluripotent, developmental, and ecto-mesenchymal genes is relatively close to that of iPS and embryonic stem (ES) cells. Among these genes, it is found that overexpression of PAX9 and knockdown of HERV-FRD improved the efficiencies of iPS generation.

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