Researcher Uses Hair Follicle as Window
to Understanding Organ Regeneration
By Matthew Busse | February 21, 2006
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Normal (wild type) mouse (left) and its
littermate (right) in which a transcription factor was expressed in the skin stem cells causing a loss of hair and thickening of the skin. |
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When Colin Jamora was a graduate student at UCSD in 1999, regenerative medicine—using stem cells to regenerate organs or tissue—was a relatively unheard of concept. But a scientific paper about liver regeneration piqued his curiosity.
What stuck him was the fact that up to two thirds of the liver could be removed and would grow back to its original size and shape. From that point, he was determined to understand why some organs, such as the liver and skin, are capable of regeneration while most are not.
After a post-doctoral fellowship at The Rockefeller University in New York, Jamora returned to UCSD to establish his own lab, investigating the formation of hair follicles and the regenerative cycle of hair growth and loss in mice. He chose to study the hair follicle for several reasons. For starters, hair is not essential, which is important because a common way to study any process in biology is to make genetic alterations to the process and observe the effects.
In vital organs such as the liver, these alterations can lead to the death of the animal, which yields little valuable information. Since hair is not absolutely vital to the survival of a mouse, researchers can perturb the development of the hair follicles and observe the effects, allowing them to gain detailed insights into how the process normally works.
“The animal can tolerate hair loss, so we can do really good genetics and the animal doesn’t really care,” says Jamora. And unlike internal organs, hair grows on the outside of the body, meaning it is easy to observe the effects of genetic changes. “You can just look at the animal without having to do surgery or use other invasive means.”
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| Histological section of the transgenic skin in which the transcription factor was expressed in certain epidermal stem cells. The area to the left of the arrow is normal skin and to the right is a section with stem cells expressing the transcription factor Snail leading to massive proliferation of the cells and thickening of the epidermis. Epi = epidermis, der = dermis, hf= hair follicle and the dotted line notes the separation of the epidermis from the dermis. |
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Ultimately, Jamora hopes to understand what is unique about the hair follicle that allows it to regenerate. During the development of an animal, all organs undergo a process known as morphogenesis, when a uniform layer of stem cells changes into all the different cell types that make up an organ. The early steps of this morphogenesis are similar for all organs, even though the end result is very different. For some reason, organs that can regenerate are able to reinitiate a process similar to morphogenesis later in life.
“As we get a better understanding of this process in hair follicles, we can see what’s missing in other organs,” says Jamora. Since the basic program of morphogenesis is similar in all organs, insights gained in the hair follicle can probably be applied to all other organs.
Specifically, Jamora hopes to better understand what causes the stem cells of the skin to turn into hair follicles. The epidermal stem cells found in skin have two options: They can either remain stem cells or they can change and grow into a skin cell, a hair follicle or an oil gland.
“The focus of the lab,” according to Jamora, “is to understand the basics of how stem cells are specified, and how changes in cell morphology are coordinated to generate specific structures.” Biological signals from surrounding cells help the stem cells to make these choices. “We’re trying to dissect out the individual signaling pathways, and more importantly, how they work in concert with other signals to specify select cells,” he adds.
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