Biological importance of OCT transcription factors in reprogramming and development

Abstract

Ectopic expression of Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs). Attempts to identify genes or chemicals that can functionally replace each of these four reprogramming factors have revealed that exogenous Oct4 is not necessary for reprogramming under certain conditions or in the presence of alternative factors that can regulate endogenous Oct4 expression. For example, polycistronic expression of Sox2, Klf4 and c-Myc can elicit reprogramming by activating endogenous Oct4 expression indirectly. Experiments in which the reprogramming competence of all other Oct family members tested and also in different species have led to the decisive conclusion that Oct proteins display different reprogramming competences and species-dependent reprogramming activity despite their profound sequence conservation. We discuss the roles of the structural components of Oct proteins in reprogramming and how donor cell epigenomes endow Oct proteins with different reprogramming competences.

Fig. 1. iPSCs can be generated by direct or indirect activation of endogenous Oct4.

a Direct activation of endogenous Oct4 by Oct4 upstream genes or chemical compounds. b Indirect activation of endogenous Oct4 by lineage specifiers or polycistronic expression of Sox2, Klf4, and c-Myc.