Differential effects of recombinant fusion proteins TAT-OCT4 and TAT-NANOG on adult human fibroblasts

Abstract

OCT4 and NANOG are two important transcription factors for maintaining the pluripotency and self-renewal abilities of embryonic stem (ES) cells. Meanwhile they play key roles in the induced pluripotent stem (iPS) cells. In this study, recombinant transcript factors TAT-NANOG and TAT-OCT4, which contained a fused powerful protein transduction domain (PTD) TAT from human immunodeficiency virus (HIV), were produced. Each fusion protein could be transported into human adult fibroblasts (HAF) successfully and activated the endogenous transcription of both nanog and oct4. Our study revealed the inter-regulation and autoregulation abilities of solo oct4 or nanog in the process of iPS cell reprogramming. Meanwhile the transduction of TAT-NANOG could accelerate the growth rate of HAF cells, and the key cell cycle regulator cdc25a was up-regulated. Thus cdc25a may be involved in the regulation of cell growth by NANOG. In addition, the TAT fusion protein technology provided a novel way to improve cell growth that is more controllable and safer.

Key words： induced pluripotent stem cells (iPS cells); OCT4; NANOG; protein transduction domain; TAT; cell proliferation

Acknowledgements

This work was supported by grants from the Ministry of Science and Technology of China (No. 2006CB943601) and the Natural Science Foundation of China (Grant No. 90919042).

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