The Molecular Circuitry Underlying Pluripotency in Embryonic and Induced Pluripotent Stem Cells

Abstract Pluripotency is maintained through a complex network of signaling pathways that interact with transcription factors including octamer binding protein 4, SRY- box 2 , and Nanog, chromatin modifying complexes, microRNAs, and the DNA structure itself to preserve the undifferentiated, self-renewing state. Whereas the signaling requirements for the maintenance of stem cells can vary by species of origin, state of the stem cells, and culturing conditions, the core transcriptional circuity activated and maintained by these pathways is highly conserved. The self-sustaining nature of the pluripotency network is evident in the finding that somatic cells can be reprogrammed to a pluripotent state through the transient introduction of a small group of factors, which serve to reestablish the stem cell signaling and transcriptional network. Growing understanding of the molecular circuitry of pluripotency has major implications for the field's view of developmental biology and disease pathogenesis and is important for the evolving field of regenerative medicine.