Epidermal Stem Cells Can Reverse Their Fate in Developm*

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DESCRIPTION (provided by applicant): Homeostasis of continuously renewing adult tissues, such as the epidermis and the hematopoietic system, is maintained by somatic stem cells. These are undifferentiated, s elf-renewing cells, which also produce daughter transient amplifying (TA) cells. TA cells undergo a finite number of cell divisions before differentiating and leaving the proliferative compartment, whereas the stem cells persist throughout the lifetime of the organism [1]. We first directly demonstrated heterogeneity in the proliferative cells of the epidermis in 1981 when we identified a small cells [2]. Recently, we developed a sorting method that yields a viable population of somatic stem cells from mouse epidermis [3]. We showed that these stem cells have the capacity to regenerate the epidermis and to permanently express a recombinant gene in the regenerated tissue. A few years ago it was demonstrated that somatic stem cells have the remarkable capacity to differentiate into other tissue types [4], and have a plasticity only expected of embryonic stem cells. Our preliminary data suggest that this may also be true for epidermal stem cells, and that they have the ability to differentiate into both ectodermally- and mesenchymally-derived tissues, suggesting that somatic epidermal stem cells can cross the ectoderm-mesoderm developmental barrier. Therefore, our hypotheses are 1) that somatic epidermal stem cells can function in a similar manner to embryonic stem cells during development, and 2) that environmental (extrinsic) factors influence the developmental pathway for somatic stem cells. To test these hypotheses, we propose 1) To determine whether epidermal stem cells injected into blastocysts alter their phenotype during development, and 2) to determine whether the injected epidermal stem cells permanently function as part of the tissue or organ in which they reside.