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Master regulatory gene found that guides fate of blood-producing stem cells

at all the immature, leukemic cells differentiate and die.

Over the past 10 years, several gene families have been suggested to be important in regulating HSC fate-for example homebox, wnt, notch 1, and telomerase genes. Emerson and colleagues figured that one transcription factor, called NF-Y, was required for activating promoters of all of these genes. What's more, they found that fully assembled NF-Y was activated in stem cells and disappeared when the stem cells became mature cell types, through the induction and loss of one its subunits, NF-Ya.

"When we overexpressed NF-Ya in stem cells, the stem cells produced ten- to twenty-fold more stem cells after transplantation," says Emerson. "This makes NF-Ya the prime candidate for a master-regulatory gene for multiple, if not all, stem-cell division programs." NF-Ya would be considered the master regulatory gene since it activates multiple HSC regulatory genes and promotes HSC self-renewal.

Practically, the researchers' goal is to find a way to control stem-cell fate by biochemically turning NF-Ya on or off at will, to either make more stem cells in the case of bone-marrow failure and for transplantation, or to force the cells to differentiate, in the case of leukemia, where too many HSCs are made.


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Source:University of Pennsylvania School of Medicine


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