How mechanical forces affects the way stem cells divide

Stem cells have the capability to self-renew and to differentiate into more specialized progeny. They can do that by switching from an asymmetric mode of cell division, where one stem cell gives rise to another stem cell and a differentiated cell, to a symmetric mode, where one stem cell divides into two stem cells or possibly also into two differentiated cell.

Many studies have been carried out to investigate the molecular factors controlling this transition from symmetric to asymmetric cell divisions and it is generally believed that mechanical forces play an important regulatory role.

The orientation of the cell division process is mainly due to the action of a dynamic structure called mitotic spindle, which search and capture chromosomes, assemble them at the centre of the cell and then separate them during cell division.

We investigated the role of mechanical forces in determining the spindle orientation with a simple computational model, applied on one of the most studied and well-known stem cells niches: the intestinal crypt. We used the model to simulate the development of a layered tissue, focusing on the crossover from symmetric to asymmetric stem cell divisions.

By doing that, we found that mechanical constraints affect the way stem cells divide. At first, they always divide symmetrically until the base layer of the tissue is filled completely. Then, further symmetric divisions are hindered as the horizontal compression of the layer leads to a reorientation of spindle axis along the vertical direction. At this point, the mode of division switches to an asymmetric one, with one stem cell remaining in the base layer and one differentiated cell populating the upper layers of the tissue. When compared with experimental results on mice intestinal crypt development, our simulations shown very good agreement.

Z. Bertalan, S. Zapperi and C. A. M. La Porta,
Modeling mechanical control of spindle orientation of intestinal crypt stem cells
Journal of Theoretical Biology 430, 103–108 (2017)
https://doi.org/10.1016/j.jtbi.2017.07.012