Differentiation and lineage specification of stem cells - Insights from analysing the dynamics of small-scale regulation networks

Although there are a number of quite different types of stem cells (such as embryonic, tissue, or cancer stem cells) all of them are characterised by the ability to ”decide” about the realisation of two generally different developmental pathways: self-renewing their current state or differentiating into (multiple) distinct mature cell types. Even though it is widely accepted that transcription factor regulation plays an important role in this decision process, neither the topology nor the dynamics of the regulatory networks are known at the moment.

Beside a general introduction into the biology of stem cells, my talk will focus on the discussion of an approach to model the dynamics of transcription factor interactions in stem cells on the basis of biologically motivated, small-scale networks, which are represented by systems of ordinary differential equations. I will present results on the application of such an approach to two stem cell systems, elaborating on the process of lineage specification of haematopoietic stem cells (HSC) and on the process of maintaining the undifferentiated, pluripotent ”ground state” of embryonic stem cells (ESC).