Interphase chromatin undergoes a local sol-gel transition upon cell differentiation
Cell differentiation, the process by which stem cells become specialized cells, is associated with chromatin reorganization inside the cell nucleus. Here, we measure the chromatin distribution and dynamics in embryonic stem cells in vivo before and after differentiation. We find that undifferentiated chromatin is less compact, more homogeneous and more dynamic than differentiated chromatin. Further, we present a noninvasive rheological analysis using intrinsic chromatin dynamics, which reveals that undifferentiated chromatin behaves like a Maxwell fluid, while differentiated chromatin shows a coexistence of fluid-like (sol) and solid-like (gel) phases. Our data suggest that chromatin undergoes a local sol-gel transition upon cell differentiation, corresponding to the formation of the more dense and transcriptionally inactive heterochromatin [Eshghi et al., Phys. Rev. Lett., 2021]. In addition, we present a hydrodynamic-based computational model of the human genome that suggests that euchromatin activity enhances heterochromatin segregation and compaction in the cell nucleus [Mahajan A et al., Phys. Rev. X, 2022].