The Role of β-catenin in Embryonic Stem Cell Maintenance Circuits and iPSCs - An International Systems Biology Approach of Open Science and Innovation

Embryonic stem cells (ESCs) and induced pluripotent stem cell (iPSCs), i.e. somatic body cells reprogrammed into ESCs, are the most powerful sources of regenerative medicine. Pluripotency of iPSCs and ESCs bears the capacity to enable all possible cell and organ replacement strategies for regenerative and rejuvenating medicine. This cellular ability is unique and maintained under self-renewal culture propagation conditions that enable intracellular signaling mediators to stabilize the molecular circuits and functions of pluripotency via transcriptional and epigenetic mechanisms inter alia. Understanding these sustained networks that auto-equilibrate in steady states of reciprocatively regulated pluripotency factors that globally organize the stemness genome, transcriptome, and proteome, is crucial for future strategies of regenerative medicine. All stem cells are regulated by such stemness and differentiation circuits and ESC pluripotency is still their best model system. A self-sustaining network of transcriptional activators and repressors specifies the undifferentiated identity and gatekeeps differentiation via hierarchical master regulators like Oct-3/4, Nanog, Sox-2, and Klf-4 at its core. These factors are of the highest functional-regulatory order and can even globally reprogram specialized body cells into iPSCs.