Pluripotent cells have unique properties of self-renewal while maintaining developmental potential to differentiate into all three germ layers. By definition, pluripotent cells have no predetermined lineage program, thereby forming the fundamental basis of enquiry and experimental investigations to understand cell fate decisions. Molecular and cellular insights into human pluripotent stem cell (hPSC) fate hold the potential to impact a broad range of human disease for cell replacement therapies and disease modeling and therefore are highly prioritized in current research efforts. The majority of concepts regarding ground state pluripotency have been derived from large-scale genomic, epigenomic and proteomic experimentation using a variety of hPSC lines cultured and derived from very divergent culture and derivation methods. In turn, these global analyses are unique to the human and differ from sources used for the study of mouse ESCs or iPSCs, which are derived from inbreed strains and standardized culture conditions. Although this provides consistent results using mouse PSCs, the surrogacy that can be translated to hPSCs to improve differentiation toward applications is completely unclear. Nevertheless, commonality in pluripotent state emerges from a core set of transcription factors, including Oct4, Sox2 and Nanog. Unique to hPSCs, these factors regulate pluripotency by associating with epigenetic (e.g., Polycomb and Trithorax) regulators to establish bivalent marks. However, the complex interplay among transcription factors, cell signaling and bivalent epigenetic marks has not yet been fully described in the context of hPSC differentiation.
展开▼
