Research Fellows Directory
Dr Pablo Navarro
University of Edinburgh
Embryonic Stem (ES) cells present a paradox because they can both self-renew and differentiate into all adult cell types, a characteristic termed pluripotency. Indeed, it is the possession of these seemingly incongruent properties that defines ES cells and makes them useful, both for addressing developmental questions and for regenerative medicine approaches. A full biological understanding of the molecular basis of such paradoxical properties is essential to gain the complete control over pluripotent cells required to maximally harness the promise they hold.
Nanog is a critical factor of ES cell biology. First identified by its ability to block differentiation pathways of ES cells by maintaining them in an undifferentiated and self-renewing state, Nanog was then shown to be expressed in a mosaic manner. Indeed, although genetically identical, individual ES cells within a given population express different doses of Nanog, with the cells expressing the lower levels being more likely to differentiate, and those expressing higher levels displaying high self-renewal efficiencies. Importantly, individual cells possess the ability to transit from one state to the other and therefore have, at a given time-point, variable access to alternate fates.
What now emerge as critical gaps in our knowledge that we must understand in order to better describe, model and ultimately control ES cell behaviour, are the means by which Nanog fluctuations first arise, and then direct altered cellular functions. These questions are important in order to provide the significant new understanding necessary to move the field forward. Answers to these questions may illuminate the fundamental paradox of stem cells: how individual cells can do one thing (self-renew) while maintaining the capacity to do another mutually exclusive thing (differentiate).
Interests and expertise (Subject groups)