The real reason behind goosebumps

If you’ve ever wondered why we get goose bumps, you’re in good company, as is Charles Darwin, who reflected on them in his writings on evolution. Goosebumps might protect thick-skinned animals from the cold, but humans don’t seem to benefit much from the reaction, so why has it been preserved throughout evolution all this time?

In a new study, scientists at Harvard University discovered the reason: The types of cells that cause goosebumps are also important in regulating stem cells that regenerate the hair follicle and hair. Beneath the skin, the muscle that contracts to create goose bumps is necessary to link the sympathetic nerve connection to the hair follicle stem cells. The sympathetic nerve reacts to the cold by contracting the muscle and causing chills in the short term, and by driving the activation of hair follicle stem cells and the growth of new hair in the long term.

Published in the magazine CellThese findings in mice give researchers a better understanding of how different cell types interact to link stem cell activity to changes in the external environment.

“We have always been interested in understanding how stem cell behaviors are regulated by external stimuli. The skin is a fascinating system: it has multiple stem cells surrounded by various types of cells and it is at the interface between our body and the outside world” . Therefore, their stem cells could respond to a wide variety of stimuli, from the niche, the entire body, or even the outside environment, “said Ya-Chieh Hsu, associate professor at Alvin and This Star for stem cell and regenerative biology, who led the study in collaboration with Professor Sung-Jan Lin of National Taiwan University. “In this study, we identified an interesting two-component niche that not only regulates stem cells in steady state, but also modulates the behavior of stem cells according to changes in outside temperature. “

A system to regulate hair growth.

Many organs are made up of three types of tissue: epithelium, mesenchyme, and nerve. On the skin, these three lineages are organized in a special arrangement. The sympathetic nerve, part of our nervous system that controls the body’s homeostasis and our responses to external stimuli, connects to a small smooth muscle in the mesenchyme. This smooth muscle in turn connects to hair follicle stem cells, a type of epithelial stem cell critical to regenerate the hair follicle and repair wounds.

The connection between the sympathetic nerve and muscle is well known, as they are the cellular basis behind goosebumps: the cold causes sympathetic neurons to send a nerve signal, and the muscle reacts by contracting and causing hair to stand on end. However, by examining the skin at extremely high resolution using electron microscopy, the researchers found that the sympathetic nerve not only associated with muscle, but also formed a direct connection to hair follicle stem cells. In fact, nerve fibers wrap around the hair follicle stem cells like a ribbon.

“We were really able to see at the ultrastructure level how the nerve and stem cells interact. Neurons tend to regulate excitable cells, like other neurons or muscles with synapses. But we were surprised to find that they form synapse-like structures with an epithelial stem cell , which is not a very typical target for neurons, “said Hsu.

The researchers then confirmed that the nerve did indeed target the stem cells. The sympathetic nervous system is normally activated at a constant low level to maintain the body’s homeostasis, and the researchers found that this low level of nerve activity kept stem cells in a state ready for regeneration. Under prolonged cold, the nerve activated at a much higher level and more neurotransmitters were released, causing stem cells to activate quickly, regenerate the hair follicle, and develop new hair.

The researchers also investigated what maintained nerve connections with hair follicle stem cells. When the muscle connected to the hair follicle was removed, the sympathetic nerve retracted, and the nerve connection to the hair follicle stem cells was lost, demonstrating that the muscle was a necessary structural support to attach the sympathetic nerve to the hair follicle.

How the system develops

In addition to studying the hair follicle in its fully formed state, the researchers investigated how the system initially develops – how the muscles and nerves reach the hair follicle in the first place.

“We found that the signal comes from the developing hair follicle itself. It secretes a protein that regulates smooth muscle formation, which then attracts the sympathetic nerve. Then, in the adult, the interaction spins, with the nerve and muscle together. Regulates hair follicle stem cells to regenerate the new hair follicle. It’s closing the whole circle – the developing hair follicle is establishing its own niche, “said Yulia Shwartz, a postdoctoral fellow in Hsu’s lab. She was co-first author of the study, along with Meryem Gonzalez-Celeiro, a graduate student at the Hsu Laboratory, and Chih-Lung Chen, a postdoctoral fellow at the Lin Laboratory.

Responding to the environment

With these experiments, the researchers identified a two-component system that regulates hair follicle stem cells. The nerve is the signaling component that activates stem cells through neurotransmitters, while muscle is the structural component that enables nerve fibers to connect directly with stem cells of the hair follicle.

“It can regulate hair follicle stem cells in many different ways, and they are wonderful models for studying tissue regeneration,” said Shwartz. “This particular reaction is helpful in coupling tissue regeneration with changes in the outside world, such as temperature. It is a two-layer response: goosebumps are a quick way to provide some sort of short-term relief. But when the cold lasts, this becomes a good mechanism for stem cells to know that it may be time to regenerate the new coat. “

In the future, researchers will further explore how the external environment could influence skin stem cells, both under homeostasis and in repair situations such as wound healing.

“We live in a constantly changing environment. Since the skin is always in contact with the outside world, it gives us the opportunity to study what mechanisms stem cells use in our bodies to integrate tissue production with changing demands, which it is essential for organisms to thrive in this dynamic world, “said Hsu.