Biological importance of OCT transcription factors in reprogramming and development

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. Stem cells: Mechanisms for reprogramming cells Cells can be reprogrammed into induced pluripotent stem cells (iPSCs), embryonic-like stem cells that can turn into any cell type and have extensive potential medical uses, without adding the transcription factor OCT4. Although other nearly identical OCT family members had been tried, only OCT4 could induce reprogramming and was previously thought to be indispensable. However, it now appears that the reprogramming can be induced by multiple pathways, as detailed in a review by Hans Scholer, Max Planck Institute for Biomolecular Medicine, Munster, and Johnny Kim, Max Planck Institute for Heart and Lung Research, Bad Nauheim, in Germany. They report that any factors that trigger cells to activate endogeous OCT4 can produce iPSCs without exogeously admistration of OCT4. The mechanisms for producing iPSCs can differ between species. These results illuminate the complex mechanisms of reprogramming.

Automated summary

The ectopic expression of Oct4, Sox2, Klf4 and c-Myc can reprogram somatic cells into induced pluripotent stem cells (iPSCs), with Oct4 not always being necessary for reprogramming. Different Oct family members and species display varying reprogramming capacities, indicating a complex mechanism for reprogramming. Epigenomes of donor cells can affect the reprogramming competence of Oct proteins.