Lee Jungwoon, Lee Jinhyuk, Cho Yee Sook
Stem Cell Research Laboratory, Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
J Clin Med. 2018 Nov 27;7(12):488. doi: 10.3390/jcm7120488.
The pharmaceutical compounds that modulate pluripotent stem cell (PSC) identity and function are increasingly adopted to generate qualified PSCs and their derivatives, which have promising potential in regenerative medicine, in pursuit of more accuracy and safety and less cost. Here, we demonstrate the peroxisome proliferator-activated receptor α (PPARα) agonist as a novel enhancer of pluripotency acquisition and induced pluripotent stem cell (iPSC) generation. We found that PPARα agonist, examined and selected Food and Drug Administration (FDA) -approved compound libraries, increase the expression of pluripotency-associated genes, such as Nanog, Nr5A2, Oct4, and Rex1, during the reprogramming process and facilitate iPSC generation by enhancing their reprogramming efficiency. A reprogramming-promoting effect of PPARα occurred via the upregulation of Nanog, which is essential for the induction and maintenance of pluripotency. Through bioinformatic analysis, we identified putative peroxisome proliferator responsive elements (PPREs) located within the promoter region of the Nanog gene. We also determined that PPARα can activate Nanog transcription by specific binding to putative PPREs. Taken together, our findings suggest that PPARα is an important regulator of PSC pluripotency and reprogramming, and PPARα agonists can be used to improve PSC technology and regenerative medicine.
调节多能干细胞（PSC）特性和功能的药物化合物越来越多地被用于生成合格的PSC及其衍生物，这些衍生物在再生医学中具有广阔的应用前景，旨在追求更高的准确性、安全性和更低的成本。在此，我们证明过氧化物酶体增殖物激活受体α（PPARα）激动剂是一种新型的多能性获得和诱导多能干细胞（iPSC）生成增强剂。我们发现，在重编程过程中，经检查和筛选的美国食品药品监督管理局（FDA）批准的化合物库中的PPARα激动剂可增加多能性相关基因（如Nanog、Nr5A2、Oct4和Rex1）的表达，并通过提高重编程效率促进iPSC生成。PPARα的重编程促进作用是通过上调Nanog实现的，Nanog对于多能性的诱导和维持至关重要。通过生物信息学分析，我们在Nanog基因的启动子区域鉴定出假定的过氧化物酶体增殖物反应元件（PPRE）。我们还确定PPARα可通过与假定的PPRE特异性结合来激活Nanog转录。综上所述，我们的研究结果表明PPARα是PSC多能性和重编程的重要调节因子，PPARα激动剂可用于改进PSC技术和再生医学。
