Viscoelastic Changes to Stem Cell Nuclei Helps Commit Them to A Differentiation Pathway

Viscoelastic Changes to Stem Cell Nuclei Helps Commit Them to A Differentiation Pathway

Stem cells are undifferentiated or partially differentiated cells that can turn into many different cell types in the body. They support growth and produce new specialized cells as cells die or are damaged. Stem cells are being harnessed and used in regenerative medicine to promote the repair of diseased, dysfunctional, and injured tissue, and knowledge about the biochemical triggers that lead to the differentiation of stem cells is growing, but relatively little is known about how stem cells commit to a certain differentiation pathway.

Now a team of researchers at Tokyo Metropolitan University has found that the sponginess and stickiness (viscoelasticity) of the nuclei of stem cells control how they turn into more specialized cells. The researchers found the nuclei of stem cells are initially in a solid-like state, but over time they become more fluid. That results in less force being applied to the inner parts of the cells, which allows them to commit to a specific differentiation pathway.

The researchers studied human mesenchymal stem cells, which can differentiate into a range of different cells such as bone, cartilage, muscle, and fat cells, and tested how they responded to physical stimuli. The researchers introduced inert beads into the nuclei of stem cells, which moved in response to the thermal energy surrounding them. The motion of the tiny beads was then tracked to measure the viscosity and elasticity of the nuclei of the cells, in a process termed micro-rheology.

The researchers calculated two values, storage and loss moduli, which corresponded to elasticity and viscosity, and tracked the viscoelasticity throughout the entire differentiation process. The nuclei of cells behave like viscoelastic materials, and the dynamic regulation of the viscoelastic properties of cell nuclei is critical to the differentiation process. As the stem cells moved further down their differentiation path the nuclei lost their solid-like state and became more liquid-like, and as a result, the nuclei became less susceptible to physical forces.

Imagine pushing a snooker ball compared to a sponge. The force applied to the former is transferred to the core of the ball, whereas that is much less the case with a sponge. The researchers determined that this change is largely due to the aggregation of chromatin, a complex of DNA and proteins in cell nuclei. When chromatin aggregates in cells it is thought to suppress the expression of genes. This study suggests the aggregation of chromatin is also critical to the differentiation of stem cells and ensures the cells commit to their differentiation path.

You can read more about the study in the paper – Intranuclear mesoscale viscoelastic changes during osteoblastic differentiation of human mesenchymal stem cells – which was recently published in The FASEB Journal. DOI: 10.1096/fj.202100536RR