As researchers seek ways to manipulate stem cells, which have the ability to differentiate into multiple types of tissues, one challenge they face is maintaining the stem cells in their immature state. The newly identified repressor switch could provide part of the answer.
Led by Howard Hughes Medical Institute investigator Elaine Fuchs, the researchers published discovery of this regulator, known as Tcf3, in an article in the October 6, 2006, issue of the journal Cell. Other co-authors on the paper include Hoang Nguyen and Michael Rendl in the Fuchs laboratory at The Rockefeller University.
Tcf3 is a transcription factor, a protein that controls the activity of a collection of genes in order to coordinate their action. In earlier studies, Fuchs and her colleagues had found that the gene for Tcf3 is activated in a region of the adult hair follicle called the bulge, where stem cells are expected to be. They also knew from studies in other laboratories that a relative of Tcf3, called Tcf4, appears to be important for the development of the intestine.
The researchers reasoned that if Tcf3 plays a role in maintaining adult follicle cells, it would also be present in embryonic skin, which consists mainly of stem cells. When they analyzed the epidermis of embryonic mice, they found that theTcf3 gene was, indeed, active in the embryonic skin stem cells.
The researchers next sought to pinpoint which genes Tcf3 controls. They genetically engineered a mouse in which they could switch the Tcf3 gene on at will in skin cells. They then used DNA microarrays to analyze which genes were affected when Tcf3 was activated. Microarrays, also known as "gene chips," enable scientists to determine the activity of thousands of genes at once.
"When we compared the list of genes that Tcf3 repressed or induced, we found that it was very similar to the genes expressed when the skin is embryonic," said Nguyen. "So, by turning on Tcf3, we were essentially reverting the postnatal skin cells to be more similar to embryonic skin cells. The genetic program induced by Tcf3 is also very similar to that seen in bulge cells, where adult stem cells are thought to reside," she said.
In particular, the researchers found that Tcf3 repressed members of a gene family called PPAR, which themselves produce key transcription factors that promote skin stem cells to differentiate into epidermal and sebaceous gland cells.
The biggest surprise, said Fuchs, came when the researchers analyzed how switching on Tcf3 affected the differentiation of embryonic skin stem cells. They found that activating the gene in mice blocked differentiation of all three types of mature skin cells -- epidermal, sebaceous, and hair follicle. "We've known for some time that Tcf3 can operate with a co-factor called â-catenin and initiate skin stem cells to make hair follicles. But we hadn't realized that Tcf3 could act on its own to keep skin stem cells in an undifferentiated state," Fuchs explained. â-Catenin is stabilized in response to Wnt signaling, which Fuchs' team earlier showed plays a key role in the ability of stem cells to make hair.
Fuchs said that Wnt signaling has been shown to play a role in many different types of stem cells in the body. The discovery that one of â-catenin's partners, Tcf3, can repress genes in the absence of a Wnt signal may be important in understanding how these transcription factors work in stem cells. In further studies, Fuchs and her colleagues plan to study in more detail how Tcf proteins govern stem cell biology.
Jennifer Michalowski | EurekAlert!
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
14.12.2018 | Power and Electrical Engineering
14.12.2018 | Physics and Astronomy
14.12.2018 | Physics and Astronomy