If you've ever wondered why we get goosebumps, you're not alone—Charles Darwin pondered this very question in his writings on evolution.While goosebumps may protect fur-covered animals from cold, humans seem to gain little benefit from this response. So why has it persisted throughout evolution?
In a new study on mice, researchers from Harvard University in the U.S. and National Taiwan University in China discovered the reason: the cell type responsible for goosebumps is also crucial for regulating stem cells that regenerate hair follicles and hair.Beneath the skin, the smooth muscle responsible for contracting and creating goosebumps—known as the arrector pili muscle—serves as a vital link between the sympathetic nervous system and hair follicle stem cells. The sympathetic nervous system's response to cold triggers short-term contraction of the arrector pili muscle, causing goosebumps, while also promoting long-term activation of hair follicle stem cells and new hair growth.These discoveries provide researchers with a deeper understanding of how different cell types interact, linking stem cell activity to changes in the external environment. The findings were published online in the journal Cell on July 16, 2020, in a paper titled "Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells."
"We have long been interested in understanding how stem cell behavior is regulated by external stimuli," said Ya-Chieh Hsu, co-corresponding author and associate professor of stem cell and regenerative biology at Harvard University. "The skin is a fascinating system: it harbors multiple types of stem cells surrounded by diverse cell types, and it serves as the boundary between our body and the external environment.Therefore, its stem cells may respond to diverse stimuli from the niche, the entire body, and even the external environment. In this study, we identified an intriguing dual-component niche that not only regulates stem cells under stable conditions but also modulates their behavior in response to external temperature changes."
A System Regulating Hair Growth
Many organs are composed of three tissue types: epithelium, mesenchyme, and nerve. In skin, these three tissues assemble in a unique arrangement.Sympathetic nerves, part of our nervous system, govern bodily equilibrium and responses to external stimuli. These nerves connect to tiny smooth muscles within the mesenchyme—specifically the arrector pili muscles mentioned earlier. These smooth muscles, in turn, link to hair follicle stem cells. These epithelial stem cells are crucial for hair follicle regeneration and wound repair.
The connection between sympathetic nerves and this smooth muscle is well-known, as it forms the cellular basis for goosebumps: cold triggers nerve signals from sympathetic neurons, causing this smooth muscle to contract and raise the hair.However, when examining skin at extremely high resolution using electron microscopy, these researchers discovered that sympathetic nerves not only connect to this smooth muscle but also form direct links with hair follicle stem cells. In fact, nerve fibers wrap around hair follicle stem cells like a ribbon.Neurons typically regulate excitable cells, such as other neurons or muscles, through synaptic interactions. But we were surprised to find they form synapse-like structures with hair follicle stem cells—which aren't typical targets for neurons."
Next, the researchers confirmed that sympathetic nerves do indeed act upon hair follicle stem cells.The sympathetic nervous system typically maintains a low level of constant activation to sustain bodily equilibrium. The researchers discovered that this baseline neural activity keeps hair follicle stem cells in a state of readiness for regeneration. Under prolonged cold conditions, the sympathetic nerves reach higher activation levels, releasing increased neurotransmitters that rapidly activate the stem cells. This triggers follicle regeneration and new hair growth.
The researchers also investigated what maintains the connection between the sympathetic nerves and hair follicle stem cells. When they removed the smooth muscle attached to the hair follicles, the sympathetic nerves retracted, and the connection between the nerves and the stem cells was lost. This indicates that this smooth muscle serves as the essential supporting structure linking the sympathetic nerves to the hair follicles.
How this system arises
Beyond studying fully formed hair follicles, the researchers also investigated how this system initially arises—how smooth muscle and sympathetic nerves first arrive at the follicle.It secretes a protein that regulates smooth muscle formation, which in turn attracts sympathetic nerves. In adulthood, this interaction reverses, with sympathetic nerves and smooth muscle jointly regulating hair follicle stem cells to regenerate new follicles. This closes the entire cycle—the developing hair follicle is establishing its own microenvironment."
Responding to the environment
Through these experiments, the researchers identified a two-component system regulating hair follicle stem cells.Sympathetic nerves serve as the signaling component that activates hair follicle stem cells via neurotransmitters, while smooth muscle acts as the structural component enabling direct neural fiber connection to these cells. "You can modulate hair follicle stem cells in many different ways," says Schwartz. "They make a wonderful model for studying tissue regeneration. This particular response is useful for coupling tissue regeneration to external changes like temperature."It's a two-tiered response: goosebumps provide a quick, short-term relief. But when cold persists, it becomes an effective mechanism for signaling to hair follicle stem cells that it might be time to regenerate new fur."
Moving forward, these researchers will further explore how the external environment influences stem cells in the skin, both under steady-state conditions and during repair processes like wound healing.
"We live in a constantly changing environment," Hsu said. "Because skin is always in contact with the outside world, it gives us an opportunity to study the mechanisms our stem cells use to align tissue production with evolving demands—which is crucial for organisms to thrive in this dynamic world."