How stem cells organize cellular replacements at a distance

Amazing stuff!

"... 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 ... 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 ... team ... 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. ..."

From the abstract:

"Skin homeostasis is maintained by stem cells, which must communicate to balance their regenerative behaviors. Yet, how adult stem cells signal across regenerative tissue remains unknown due to challenges in studying signaling dynamics in live mice. We combined live imaging in the mouse basal stem cell layer with machine learning tools to analyze patterns of Ca2+ signaling. We show that basal cells display dynamic intercellular Ca2+ signaling among local neighborhoods. We find that these Ca2+ signals are coordinated across thousands of cells and that this coordination is an emergent property of the stem cell layer. We demonstrate that G2 cells are required to initiate normal levels of Ca2+ signaling, while connexin43 connects basal cells to orchestrate tissue-wide coordination of Ca2+ signaling. Lastly, we find that Ca2+ signaling drives cell cycle progression, revealing a communication feedback loop. This work provides resolution into how stem cells at different cell cycle stages coordinate tissue-wide signaling during epidermal regeneration."

How stem cells organize cellular replacements | YaleNews In a new study, Yale scientists reveal insights into how stem cells communicate with one another to coordinate the replacement of lost cells.

Cell cycle controls long-range calcium signaling in the regenerating epidermis (open access)

Fig. 1 The epidermal stem cell layer cohesively carries out coordinated Ca 2+ signaling at long range.