Stem cell depletion through epidermal deletion of Rac1 (Science, 309:933-935, 5 August 2005)

報告日期: 2005/10/18
報告時間: 17:10/18:00
報告學生: 葉儀君
講評老師: 林聖哲
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Stem cell depletion through epidermal deletion of Rac1

Science, 309: 933-935, 2005

Speaker: Yi-June Yeh

        Commentator: M.D. and PhD. Sheng-Che Lin

        Date: 2005/10/18,                  Classroom: 602

 

Mammalian epidermis has limited lifespan. Keeping proliferation and differentiation of epidermal stem cell perform the normal functions of epithelium (1). However, the mechanisms of how stem cell keeps self-renew versus differentiation are unclear. Rac1 is a pleiotropic effector and is involved in multiple cellular functions, such as cell-matrix adhesion and cytoskeleton organization (2). In order to elucidate the role of Rac1 in stem cell, mice expressing K14CreER/floxed Rac1 are employed as a model system. Deletion of Rac1 by applying 4-hydroxy-tamoxifen (4OHT) to the skin, leaded to rapidly cell proliferation and differentiation in interfollicular epidermis (IFE), and sebaceous gland (SG). After 11 to 15 days, IFE cell layers were completely or partially depleted and HF bulbs were reduced. Flow cytometry results more directly shown that Rac1 deletion reduced stem cells in the bulge. These phenomena were similar in mice expressed inducible-activated c-Myc in epidermis (3). Interestingly, the immunofluorecence result shown that Myc expression was accompanied with Rac1 deletion, which implied that Rac1 exerts its functions by regulating the transcription factor, Myc. By using 4OHT-inducible Myc mutants in human keratinocyte, they proved that Rac1 inhibited Myc functions through a specific downstream protein, PAK2. These data indicated that Rac1 and Myc exert critical roles in maintaining the stem cell niches in epidermis. They also suggest that cell adhesion and cytoskeleton organization not only important for tissue organization but also play a pivotal role in cell differentiation.

 

 

References:

1.     D. M. Owens, and F. M. Watt. Contribution of strm cells and differentiation cells to epidermal tumors. Nat. Rev. Cancer 3, 444 (2003).

2.     S. Etienne-Manneville, and A. Hall. Rho GTPases in cell biology. Nature 420, 690 (2002).

3.     M. Frye, C. Gardner, E. R. Li, I. Arnold, and F. M. Watt. Role of melanoma chondroitin sulphate proteoglycan in patterning stem cells in human interfollicular epidermis. Development 130, 2793 (2003).