Short-Time Activation of Retinoic Acid PathwayLeads to Generate Naive-Like Pluripotent S tem Cells

Objective: Compared to primed pluripotent s tem cells (PSCs)that represent the prototype of pos t-implantation epiblas t cells,naïve PSCs share traits with the pre-implantation epiblas ts.These s tages of embryonic development can be imitated invitro by modulating the main signaling pathways involved inpluripotency. We have recently shown that transient activationof retinoic acid receptor gamma (RARɣ) and liver receptor homolog-۱ (LRH-۱) induces naïve pluripotency in human PSCs.Here, we further inves tigated the impact of retinoic acid (RA)to the induction of naïve-like PSCs in ۲iL medium containingLIF, and chemical inhibitors of GSK۳β and MEK ۱/۲.Materials and Methods: In this s tudy, we used RA and RARɣagonis t, CD۴۳۷, for ۴ to ۵ days to induce primed PSCs intothe naïve s tate. The successful conversion was examined morphologicallyand by immunos taining for some naïve-specificmarkers.Results: The result revealed that the short-term treatment withCD۴۳۷ or RA causes the formation of naïve-like PSCs. The resultingcells had dome-shaped morphology and were insensitiveto single-cell dissociation and ROCKi independent. Thesecells also showed NANOG expression and nuclear localizationof TFE۳.Conclusion: Our results displayed that temporary activation ofthe RA signaling pathway in combination with ۲iL resulted inthe induction of naïve-like pluripotency in human PSCs. Theseresults highlight the function of RA signaling in pluripotency.

کلیدواژه ها:

Naïve Pluripotency ، Pluripotent S tem Cell ، RetinoicAcid ، Retinoic Acid Receptor Gamma (RARɣ)