Heme oxygenase -1 gene regulation and function in embryonic stem cells

PETRONE VICTORIA, TORO AYELEN, VAZQUEZ ECHEGARAY CAMILA, FRANCIA MARCOS, VAZQUEZ ELBA, GUBERMAN ALEJANDRA

Congreso; Xth meeting of the Latin American Society for Developmental Biology (LASDB); 2019

Embryonic stem cells (ESCs) have theability to differentiate into cells of all three germ layers and possessseveral mechanisms that ensure genome stability avoiding the propagation ofgenetic damage. Heme oxygenase (HO) is the limiting enzyme in heme catabolism,and the inducible isoform HO-1 is known by its antioxidant and antiapoptotic functions.It was reported that HO-1 is involved in ESCs differentiation; however, itsrole in this process remains unknown. We have previously found that HO-1 isexpressed in ESCs, localize both in nucleus and cytoplasm and is induced duringdifferentiation. We also found that Oct4, one of the essential pluripotency transcriptionfactors (TFs), negatively modulates HO-1 gene transcription. Our aim is toexplore HO-1 role in pluripotent stem cells and its putative involvement in generegulation. In this work, to further study HO-1 gene regulation, we evaluated theresponse of a HO-1 promoter reporter to pluripotency TFs. Consistently with HO-1gene induction during differentiation; we found that HO-1 promoter is repressedby Oct4 and Nanog. Moreover, to explore the role of HO-1 in ESCs, we are modulatingit both pharmacologically and genetically and evaluating the effect on theexpression of pluripotency TFs. As a whole, our findings suggest that HO-1could be relevant to leave behind the undifferentiated state or to initiate aspecific differentiation process. These results could reveal a novel role ofHO-1, besides its classical function.