How stem cells organize cellular replacements

Every day stem cells in the human body help replace billions of cells lost in the regular, homeostatic maintenance of our organs. But while scientists have investigated the cellular regulators of this balanced cycle of production-and-loss for years, it has remained unclear whether stem cells located in different areas of our tissues are able to communicate with each other across distances, telling each other where and how many cells need to be replaced.

In a new study, published in the Journal of Cell Biology, Yale scientists combined advanced imaging with machine learning to show that adult stem cells in skin tissue are able to coordinate calcium signals at surprisingly long distances to prompt the replacement of lost cells.

The Yale team — which was led by first authors Drs. Jessica Moore, Dhananjay Bhaskar, and Feng Gao — found that localized groups of up to 10 stem cells initiate communication via calcium signals. As seen in this video (above), these small groups of stem cells, located in a thin layer of the skin known as the epithelial tissue (labelled with magenta with calcium levels in green fluorescence), launch coordinated tissue-wide communications which dictate where and when lost cells are replaced.

This biological insight was made possible by a computational method known as “Geometric Scattering Trajectory Homology,” developed by the research team, which captures the patterns of signaling at multiple spatial and temporal resolutions. This method is broadly applicable, and the researchers are now applying it to decipher additional complex signaling in various other biological systems in a follow-up paper.

This work was carried out in the labs of Drs. Valentina Greco and Smita Krishnaswamy, both of the Yale School of Medicine (YSM), in collaboration with Drs. Caroline Hendry and Andy Cox, also at YSM.