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
Source:Howard Hughes Medical Institute