Crucial gene found for embryonic stem cell maintenance

Scientists from the University of Pennsylvania School of Medicine have identified a gene necessary for the normal progression of early mammalian embryogenesis and the establishment of embryonic stem cell lines. This work represents a significant advance in our understanding of the complex genetic framework that supports early mammalian development and stem cell pluripotency.

Critical to the use of embryonic stem cells in therapeutic applications is a thorough understanding of the genetic factors that regulate stem cell fate and preserve the delicate balance between the maintenance of a pluripotent cell population and the differentiation of more specialized cell types. In the October 15th issue of Genes & Development, Dr. Patricia Labosky and colleagues add Foxd3 to the short, but growing list of genes essential for the establishment, maintenance, and differentiation of embryonic stem cells.

Dr. Labosky and colleagues genetically engineered mice to lack Foxd3, and then analyzed the mice to determine the physiological role of the gene and its encoded protein. Foxd3-deficient embryos died early in development (around day 6.5) due to an inability of the inner cell mass to expand normally, and thereby form the embryo proper and some of the supportive extraembryonic tissues (ie., allantois and amnion). The researchers also found that embryonic stem cells, which are derived from the inner cell mass, could not be generated from Foxd3-deficient mouse embryos.

Further analysis by Dr. Labosky and colleagues revealed that the previously identified critical regulators of embryonic pluripotency (Oct4 and Fgf4) appear to be properly expressed in Foxd3-mutant embryos. This finding suggests that Foxd3 functions either downstream of Oct4 and Fgf4, or in a parallel pathway to regulate pluripotency in the early stages of mammalian embryogenesis. Interestingly, normal embryonic development can be restored through the addition of wild-type (genetically normal) e

Contact: Heather Cosel
Cold Spring Harbor Laboratory

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