Induced Pluripotent Stem Cells (iPSCs)​​ are somatic cells that have been reprogrammed back into a pluripotent state through specific methods. They not only open new avenues for drug development but also provide a valuable cell source for cell replacement therapies.

​Pluripotent Stem Cells (PSCs)​​ are primarily derived from the Inner Cell Mass (ICM) of the blastocyst stage or from embryos before the gastrula stage. They are considered the cell type with the highest developmental potential in current cell culture technologies due to their unique ability to differentiate into any tissue type within an organism. However, the process of reprogramming somatic cells into iPSCs requires extensive epigenetic reprogramming, which was once regarded as a nearly impossible task.

The ​Yamanaka factors, namely Oct4, Sox2, Klf4, and cMyc (collectively known as OSKM), not only induce pluripotency in the inner cell mass but are also involved in regulating subsequent cell differentiation processes. Among them, Oct4, Sox2, and Klf4 (OSK) act as pioneer transcription factors capable of binding silenced chromatin. Their pioneer activity is harnessed in iPSC technology to restore pluripotency in somatic cells in vitro.

The loss of ​Oct4​ leads to a loss of pluripotency in somatic cells. Downregulation of Oct4 does not immediately cause pluripotency loss but rather stabilizes the pluripotency regulatory network, suggesting that Oct4 has additional important functions during cell differentiation. Although Oct4 was once considered indispensable for iPSC generation, the activation of endogenous Sox2 marks the completion of pluripotency induction. Furthermore, the introduction of exogenous Oct4 can actually reduce the developmental potential of OSKM and SKM iPSCs. This further highlights the importance of in-depth investigation into Oct4's functions for advancing iPSC technology.

During mouse embryonic development, cell fate is largely determined by the 4-cell stage. Sustained high expression of Sox2 and prolonged Sox2/Oct4 binding drive the formation of the inner cell mass. There are differences between mice and humans in their reliance on Oct4 for establishing pluripotency: Oct4-knockout mouse blastocysts can still develop a Nanog+ inner cell mass, whereas human OCT4-knockout blastocysts cannot. Therefore, developing effective new strategies for inducing pluripotency in non-rodent species, particularly in humans, has become an urgent challenge for the field.

The research team led by Hans R. Schöler at the Max Planck Institute in Germany, in collaboration with Dr. Wu Guangming from Mingxun Biotechnology and other teams, published a study titled ​​"Highly cooperative chimeric super-SOX: Inducing naive pluripotency beyond species boundaries"​​ in the top-tier academic journal Cell Stem Cell. The paper provides an in-depth exploration of the aforementioned topic, with Dr. Wu Guangming from Mingxun Biotechnology contributing to a detailed analysis.