A protein roadmap to pluripotency and faithful reprogramming

Embryonic stem (ES) cells are of great interest because of their capability of unlimited self-renewal and multilineage differentiation, thus serving as a potentially unlimited source for tissue replacement in regenerative medicine. ES cells possess factors that maintain and induce pluripotency, as demonstrated by successful reprogramming of somatic cells by fusion with ES cells. Understanding the complex molecular mechanisms underlying ES cell pluripotency should illuminate fundamental properties of stem cells and the process of reprogramming. Proteomics has proven to be a powerful approach to gain insight into key intracellular signals governing ES cell self-renewal and differentiation. We have recently employed a proteomics approach to explore the regulatory protein networks in which Nanog, a fundamental ES cell transcription factor, operates and have constructed the first protein interaction network in mouse ES cells. The network is highly enriched for factors known to be critical in ES cell biology and appears to function as a module for pluripotency. Here we will review current ES cell proteomic studies and provide insights into how a pluripotency protein network will advance recent efforts in cellular reprogramming.