Nuclear and chromatin architecture changes accompanying differentiation

Rui Pires Martins
Centre for Academic and Professional Development
Queen Mary University of London
Presented in the Embryo Physics Course,  February 26, 2014


Pluripotency in mouse embryonic stem cells (ESCs) is thought to contain two states. The  pluripotent ground state, characterised by high levels of bi-allelic expression of the nanog  gene, and the primed state, where Nanog levels are comparatively lower and low expression of early differentiation markers for all germs layers can be detected. The subsequent state involves commitment to a particular lineage, upregulating the requisite genes to promote that programme, while downregulating pluripotency genes. In keeping with these three states, ESCs undergo changes in mechanical properties, vis a vis a changes in overall nuclear deformation and chromatin mobility. The naïve ground state is characterised by stiff, non-deformable nuclei, that soften and become quite deformable, both at the level of the whole nucleus, as well as in terms of chromatin mobility, in the primed state. Whereas these pluripotent stages are characterised by lamina containing only A-type lamins, upon differentiation, A-type lamins are expressed. As primed nuclei transition to differentiation, they begin to express A-type lamins and become more stiff, though not necessarily as stiff as in the ground state. The mobile nature of the chromatin is also lost with differentiation, as cells of more limited developmental capacity (neural stem cells, NSCs, and embryonic fibroblasts) have less mobile chromatin, preserving the 3D relationships between adjacent chromosome territories, the chromosome neighbourhoods, were preserved with differentiation. While the stiffness of the nucleus is heavily affected by A-type lamin constituents of the lamina, other factors such as the level of chromatin condensation can severely augment the  mechanical properties of nuclei.





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