Follicle Stem Cells Done in by Neighbors

Regressing tip of a hair follicle with a dying stem cell (in red) being eaten by its neighbor (in green). Photo courtesy of Kailin Mesa and Valentina Greco.

Regressing tip of a hair follicle with a dying stem cell (in red) being eaten by its neighbor (in green). Photo courtesy of Kailin Mesa and Valentina Greco.

Hairs on your body are constantly growing, dying, and regenerating from the same follicles. This process is driven, in part, by fast-dividing hair follicle stem cells. But after a hair is done growing, the extra follicle stem cells that made it die, leaving just a few alive. A new paper published by Kailin Mesa, Valentina Greco, and colleagues at Yale Cancer Center in the latest issue of Nature found a surprising culprit behind these cell deaths—the neighbors.

Scientists postulated that after a period of growth, the follicle stem cells eventually become exhausted and die, leaving just a few stem cells behind. To get a closer look, Mesa and Greco developed an ingenious intravital microscopy technique in their lab that allowed them to track individual stem cell behavior in the fur of living mice. To their surprise, it wasn’t the follicle stem cells that caused their own death, Mesa said, “It was the cells in the neighboring environment that were triggering the stem cells to die.”

Another surprising result involved the disposal of the dead stem cells. It was believed that once the stem cells died, cells from the immune system would migrate to the follicle to clear them up. “We didn’t see the [dead cell] debris ever leaving the hair follicle, which was strange. We were waiting for [the debris] to be taken up from immune cells, but we realized it doesn’t have to leave, neighboring stem cells can act as phagocytes to clear it,” Mesa explained.

Greco says she chose to focusher lab on the skin, “because it’s so external, it allows us to do live imaging, which has the potential to answer questions that have been around for a century, but were limited by tools.” Mesa added, “It provides this perfect model system where the structure of the hair follicle is very defined, and every hair follicle is the same, so we know how many stem cells there should be. We can easily see changes if we perturb the system.”

Knowing that the cell’s environment, not the cells themselves, is so important for cell death could lead to new directions for therapies for alopecia (an autoimmune disease that leads to hair loss) and cancer, according to Greco and Mesa. “Though we hope our research is useful [to those investigating therapies],” Greco says that their research will stay focused on discovering fundamental mechanisms of cells.

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Christina Szalinski is a science writer with a PhD in Cell Biology from the University of Pittsburgh.