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The hair-raising reason for goosebumps

雞皮疙瘩產生的原因

The same cell types that cause goosebumps are responsible for controlling hair growth

引起雞皮疙瘩的細胞同時也負責控制頭發的生長

If you've ever wondered why we get goosebumps, you're in good company -- so did Charles Darwin, who mused about them in his writings on evolution. Goosebumps might protect animals with thick fur from the cold, but we humans don't seem to benefit from the reaction much -- so why has it been preserved during evolution all this time?

如果你曾經思考過為什么人會產生雞皮疙瘩，那么你有伴了，因為查爾斯?達爾文在其關于進化論的著作中也曾經思考過這一問題。

In a new study, Harvard University scientists have discovered the reason: the cell types that cause goosebumps are also important for regulating the stem cells that regenerate the hair follicle and hair. Underneath the skin, the muscle that contracts to create goosebumps is necessary to bridge the sympathetic nerve's connection to hair follicle stem cells. The sympathetic nerve reacts to cold by contracting the muscle and causing goosebumps in the short term, and by driving hair follicle stem cell activation and new hair growth over the long term.

在一項新的研究中，哈佛大學的科學家們發現了雞皮疙瘩產生的原因：引起雞皮疙瘩的細胞類型在調節能夠產生虹毛囊和頭發的干細胞中也扮演著重要的作用。在皮膚下方，通過收縮以形成雞皮疙瘩的肌肉在將交感神經和虹毛囊干細胞連接起來發揮著必不可少的作用。在遇到寒冷時，交感神經會收縮肌肉并引起雞皮疙瘩短期出現。此外，交感神經還會驅使虹毛囊干細胞激活并使新的頭發長期生長。

Published in the journal Cell, these findings in mice give researchers a better understanding of how different cell types interact to link stem cell activity with changes in the outside environment.

根據發表于期刊《細胞》的這些論文，針對老鼠所做出的研究結果讓研究人員更好地了解到不同細胞類型是如何交互作用以及是如何通過這種交互作用使干細胞的活性和外界環境的變化聯系起來。

"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."

“我們一直對了解外界刺激調節干細胞的行為方式感興趣。皮膚是一個非常迷人的系統：它有數個干細胞，干細胞周圍是各種類型的細胞。而且，皮膚還位于身體和外界環境之間。因此，干細胞能夠對各種類型的刺激發生反應-從小生境，到整個身體，或甚至是外界”，Ya-Chieh Hsu,干細胞和再生生物學Alvin和Esta明星副教授表示。Ya-Chieh和國立臺灣大學的Sung-Jan Lin教授共同合作并是這一研究的帶頭人。

A system for regulating hair growth

頭發生長調節系統

Many organs are made of three types of tissue: epithelium, mesenchyme, and nerve. In the skin, these three lineages are organized in a special arrangement. The sympathetic nerve, part of our nervous system that controls body homeostasis and our responses to external stimuli, connects with a tiny smooth muscle in the mesenchyme. This smooth muscle in turn connects to hair follicle stem cells, a type of epithelial stem cell critical for regenerating the hair follicle as well as repairing wounds.

許多器官都有三類組織構成：上皮細胞、間質和神經。在皮膚中，這三類組織以一種特別的方式被安排在一起。交感神經，我們神經系統（控制體內穩態和我們對外界刺激反應）中的一部分與間(充)質中一個非常微小平滑的肌肉相連。這一光滑的肌肉反過來與虹毛囊干細胞相聯系。虹毛囊干細胞是一種上皮干細胞，其對于再生虹毛囊以及修復傷口具有關鍵作用。

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

交感神經和肌肉之間的聯系已經眾所周知，因為它們構成了雞皮疙瘩背后的細胞基礎：寒冷會觸發交感神經元發送神經信號，肌肉通過收縮并引起汗毛直立而做出反應。然而，當利用電子顯微鏡學在極其高分辨率的圖像下檢查皮膚時，研究人員們發現，交感神經不僅與肌肉相聯系，其還與虹毛囊干細胞有直接的聯系。事實上，包括在虹毛囊干細胞周圍的神經纖維就像一條帶子。

"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.

“我們能夠在超微結構層面看到神經和干細胞是如何相互作用的。神經元傾向于調節易興奮的細胞，比如其他帶有突觸的神經元或肌肉。但我們很驚訝地發現，它們會形成類似的突觸，就像表皮干細胞的結構一樣，其并非神經元的一個典型的目標。”

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

接下來，研究人員們證實，神經確實以干細胞為目標。交感神經通常會在一個恒定的低水平下被激活，以維持身體的體內穩定。研究人員們發現，這種低水平的神經活性使干細胞保持在一種平衡的狀態下以為再生做準備。在持續的寒冷條件下，神經會在一個更高的水平層面被激活并釋放更多是神經遞質，從而引起干細胞快速激活并產生虹毛囊以及生出新的頭發。

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

研究人員還調查了是什么使神經和虹毛囊干細胞之間建立聯系。當把與虹毛囊有關聯的肌肉移除后，交感神經收回，神經與虹毛囊干細胞之間的聯系消失，這表明肌肉是必不可少的將交感神經和虹毛囊聯系在一起的結構支架。

How the system develops

系統如何發展變化

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

除了研究完全成型的虹毛囊外，研究人員們還調查了系統最初發展的方式-肌肉和神經如何在一開始到達虹毛囊。

"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.

“我們發現信號來自于正在形成的虹毛囊本身。它分泌出一種能夠調節平滑肌肉形成的蛋白，然后再吸引交感神經。隨后，在成人中，交互作用發生回轉，神經和肌肉共同調節虹毛囊干細胞以產生新的虹毛囊。這時，整個循環趨于結束--正在發展的虹毛囊創建了自己的微生態”，Yulia Shwartz，Hus實驗室內的博士生介紹到。Yulia和Meryem Gonzalez-Celeiro（Meryem是Hsu實驗室內的研究生）還有Chih-Lung Chen（Lin實驗室內的博士生）是該研究的共同第一作者。

Responding to the environment

對環境做出反應

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

通過這些實驗，研究人員發現一個擁有雙成分的系統來調節虹毛囊干細胞。神經是信號成分，其可以通過神經介質激活干細胞，而肌膚是結構成分，其允許神經纖維直接與虹毛囊干細胞連接。

"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."

Shwartz表示：“你可以通過很多不同方式調節虹毛囊干細胞，這些調節方式都是研究細胞再生的模型。這一特別的反應有助于將細胞再生和外界變化，如溫度變化聯系起來。它是一個雙層應答：雞皮疙瘩是在短期提供某種緩解手段的快速方法。但是當寒冷持續時，這將成為干細胞的一個良好機制，干細胞將知道也許現在可以產生新的毛發外層。”

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

在未來，研究人員將繼續探索外界環境將如何在體內平衡和修復情況下，比如傷口愈合方面，影響皮膚中的干細胞。

"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.

我們生活在一個不斷變化的環境中。由于皮膚往往與外界相聯系，所有我們有機會研究體內的干細胞利用什么機制來將細胞生產和變化的需求結合在一起，而這是有機體在這個充滿變化的世界中蓬勃發展的重要因素。

文章來源：科學日報   編輯：質控部