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!
Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society
127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Power and Electrical Engineering
18.01.2017 | Materials Sciences
18.01.2017 | Life Sciences