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Foxd3 gene allows stem cells to remain stem cells

(Philadelphia, PA) In the search to understand the nature of stem cells, researchers at the University of Pennsylvania School of Medicine have identified a regulatory gene that is crucial in maintaining a stem cell's ability to self-renew. According to their findings, the Foxd3 gene is a required factor for pluripotency the ability of stem cells to turn into different types of tissue in the mammalian embryo. Their research is presented in the October 15th issue of the journal Genes and Development.

"Stem cells represent a unique tissue type with great potential for disease therapy, but if we are to use stem cells then we ought to know the basis of their abilities," said Patricia Labosky, PhD, an Assistant Professor in the Department of Cell and Developmental Biology. "Among the stem cell regulatory genes, it appears that Foxd3 gene expression keeps stem cells from quickly differentiating that is, developing into different types of tissue holding back the process so that an embryo will have enough stem cells to continue developing normally."

To study the function of the Foxd3 gene, Labosky and her colleagues generated mice with an inactivating mutation in the gene, and then analyzed those mice to determine the role of the Foxd3 protein.

Foxd3-deficient embryos do not survive very long. While part of the yolk sac forms, the inner cell mass that contains all the cells that make up the body of the developing embryos fails to expand enough to produce the embryo and some of the supportive tissues. Without Foxd3, the mouse embryos simply could not maintain enough stem cells to survive a crucial point in their development.

"Our findings implicate Foxd3 as one of the few genes serving as a 'master switch' of the developing embryo," said Labosky. "These genes determine the fate of cells by turning on or off other genes in response to signals in the embryo."

Foxd3 joins previously identified genes,
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Contact: Greg Lester
lesterg@uphs.upenn.edu
215 349 5658
University of Pennsylvania School of Medicine
14-Oct-2002


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