Abstract
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.
Highlights
Pluripotent stem cells (PSCs) have unique properties of unlimited self-renewal and pluripotency to differentiate into all kinds of cell types in the body, which represent valuable biomaterial for applications in regenerative medicine [1]
peroxisome proliferator-activated receptor α (PPARα) Agonists Enhance Cellular Reprogramming to Derive induced pluripotent stem cell (iPSC)
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Summary
Pluripotent stem cells (PSCs) have unique properties of unlimited self-renewal and pluripotency to differentiate into all kinds of cell types in the body, which represent valuable biomaterial for applications in regenerative medicine [1]. The pluripotency of PSCs is tightly controlled by a network of core transcriptional regulatory factors, such as Oct, Sox, and Nanog [2,3], as well as nuclear receptors and ligand-dependent transcription factors, such as Esrrb, the Nr5A family, and Nr0b1 [4,5]. Various combinations of these transcription factors have been tested and identified for somatic cellular reprogramming to pluripotency, the four “Yamanaka factors (Oct, Sox, Klf, and c-Myc, abbreviated as OSKM)” [6,7] and other alternative factors (Oct, Sox, Nanog, and Lin28) [8]. Our findings may provide new roles for the PPARα agonist as a PSC fate controller in somatic cellular reprogramming and iPSC technology
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