Stem cell self-renewal in the mouse germline

Univ Of North Carolina Chapel Hill, Chapel Hill NC

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Abstract

DESCRIPTION (provided by applicant): The precise regulation of stem cell proliferation and differentiation is essential for tissue development and homeostasis in complex organisms. In humans, malignant proliferation of stem cells can be manifested as cancers, such as seminomas. Interestingly, many of the pathways and molecules that regulate the stem cell fate are present in divergent organisms. In the germlines of D.melanogaster and C.elegans, translational repression mediated by the Pumilio (Pum) family of proteins is crucial in maintaining the undifferentiated state of germline stem cells (GSCs). An orthologous mouse protein, Pum1, may have a similar function: we have recently observed that haploinsufficiency of Pum1 results in a decrease in fertility. Therefore, we propose that Pum1 may be required to maintain the undifferentiated state of mammalian primordial germ cells (PGCs) and GSCs, which are necessary for proper development of the germline. The goal of this proposal is to characterize the function of Pum1 in gametogenesis in order to understand how stem cells are regulated in development and disease.