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If you’ve any curiosity about why we get goosebumps, then you’re in good company with some admirable people – like Charles Darwin, who considered them in his works on development. Goosebumps may protect the animals by shield creatures with thick hide from the cold, however, we people don’t appear to profit by the response much – so why has it been safeguarded during evolution all this time?
In another research, Harvard University researchers have found the explanation: the cell types that cause goosebumps are likewise significant for controlling the stem cells that regenerate the hair follicle and hair. Underneath the skin, the muscle that contracts to make goosebumps is important to connect the sympathetic nerve’s association with hair follicle stem cells. The sympathetic nerve responds to cold by getting the muscle and causing goosebumps in the short term, and by driving hair follicle stem cell activation and new hair development over a long time.
Published in the journal Cell, these discoveries in mice give researchers a superior understanding of how extraordinary cell types interact to connect stem cells action with changes in the outside condition.
“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 diverse cell types, and is located at the interface between our body and the outside world. Therefore, its stem cells could potentially respond to a diverse array of stimuli — from the niche, the whole body, or even the outside environment,” said Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology, who led the study in collaboration with Professor Sung-Jan Lin of National Taiwan University. “In this study, we identify an interesting dual-component niche that not only regulates the stem cells under steady state, but also modulates stem cell behaviors according to temperature changes outside.”
A system for regulating hair growth
Organs are made of three kinds of tissue: epithelium, mesenchyme, and nerve. In the skin, these three lineages are organized in a special arrangement. The sympathetic nerve, some portion of our nervous system that controls body homeostasis and our reactions to external stimuli, interfaces with a tiny smooth muscle in the mesenchyme. This smooth muscle thus associates with hair follicle stem cells, a kind of epithelial stem cells, basic for recovering the hair follicle as well as repairing wounds.
The link between the sympathetic nerve and the muscle has been notable since they are the cellular basis behind goosebumps: the cold triggers sympathetic neurons to impart a nerve sign, and the muscle responds by contracting and making the hair remain on end. Be that as it may, while looking at the skin under extremely high resolution using electron microscopy, the analysts found that the sympathetic nerve-related with the muscle, yet additionally framed an immediate association with the hair follicle stem cells. Actually, the nerve filaments folded over the hair follicle stem cells like a lace.
“We could really see at an ultrastructure level how the nerve and the stem cell interact. Neurons tend to regulate excitable cells, like other neurons or muscle with synapses. But we were surprised to find that they form similar synapse-like structures with an epithelial stem cell, which is not a very typical target for neurons,” Hsu said.
Next, the analysts confirmed that the nerve to be sure focused on the stem cells. The sympathetic nervous system is typically initiated at a steady low level to keep up body homeostasis, and the analysts found that this low degree of nerve action kept up the stem cells in a ready state prepared for recovery. Under prolonged cool, the nerve was enacted at a much higher level and more neurotransmitters are released, making the stem cells activated rapidly, recover the hair follicle, and develop new hair.
The scientists also researched what kept up the nerve linked with the hair follicle stem cells. At the point when they expelled the muscle associated with the hair follicle, the sympathetic nerve withdrew and the nerve associated with the hair follicle stem cells was lost, indicating that the muscle was an essential basic help to connect the sympathetic nerve to the hair follicle.
How the system develops
In addition to the studying of the hair follicle in its full-grown state, the analysts researched how the system is works – how the muscle and nerve arrive at the hair follicle in the first place.
“We discovered that the signal comes from the developing hair follicle itself. It secretes a protein that regulates the formation of the smooth muscle, which then attracts the sympathetic nerve. Then in the adult, the interaction turns around, with the nerve and muscle together regulating the 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 the Hsu lab. She was a co-first author of the study, along with Meryem Gonzalez-Celeiro, a graduate student in the Hsu Lab, and Chih-Lung Chen, a postdoctoral fellow in the Lin lab.
Responding to the environment
With these investigations, the analysts recognized a two-segment framework that controls hair follicle stem cells. The nerve is the signaling part that activates the stem cells through neurotransmitters, while the muscle is the auxiliary segment that permits the nerve fibers to directly connect with hair follicle stem cells.
“You can regulate hair follicle stem cells in so many different ways, and they are wonderful models to study tissue regeneration,” Shwartz said. “This particular reaction is helpful for coupling tissue regeneration with changes in the outside world, such as temperature. It’s a two-layer response: goosebumps are a quick way to provide some sort of relief in the short term. But when the cold lasts, this becomes a nice mechanism for the stem cells to know it’s maybe time to regenerate new hair coat.”
Later on, the scientists will additionally investigate how the outside condition may impact the stem cells in the skin, both under homeostasis and in a rapid situation, for example, wound recuperating.
“We live in a constantly changing environment. Since the skin is always in contact with the outside world, it gives us a chance to study what mechanisms stem cells in our body use to integrate tissue production with changing demands, which is essential for organisms to thrive in this dynamic world,” Hsu said.
This study was supported by the New York Stem Cell Foundation, Smith Family Foundation Odyssey Award, Pew Charitable Trusts, Harvard Neuro Discovery Center, Harvard Stem Cell Institute, Harvard Medical School Dean’s Innovation Grant, American Cancer Society, National Institutes of Health, Taiwan Ministry of Science and Technology, and National Taiwan University Hospital.