Isolation and characterization of stem cell regulatory genes oct4 and stat3 from the model fish medaka

Abstract

Medaka is an excellent lower vertebrate model in stem cell biology. Analysis of sequence homology, gene structure, chromosome synteny, protein structure and expression patterns at the RNA and protein levels have led to the notion that the medaka oct4, i.e, Oloct4, indeed encodes the medaka ortholog of the prototype Oct4 first identified in the mouse. This notion is supported by revealing OlOct4 as an octamer-binding transcription factor and its promoter activity regulated in the similar way as human Oct4 promoters as well as the mouse Nanog promoter. Two transcript variants of medaka stat3 were identified. They are widely co-expressed at a similarly high in adult tissues, except in the kidney. Interestingly, overexpression of the two variants differentially regulates the transcription activity for the Oct4 and Nanog promoters. This experiment provides first evidence for molecular networking between the Stat3 signalling pathway and Oct4 as well as Nanog in controlling stemness in medaka. This study demonstrates that stemness genes are highly conserved between fish and mammals, and experimental analyses in this easy-to-do model system will provide valuable insights into also mammalian systems.