Report

Sept4/ARTS Regulates Stem Cell Apoptosis and Skin Regeneration

Science  19 Jul 2013:
Vol. 341, Issue 6143, pp. 286-289
DOI: 10.1126/science.1233029

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Stem Cells in Wound Healing

Although excessive numbers of stem cells (SCs) may increase the risk of cancer, elevated SC numbers may be desirable, at least transiently, for the promotion of tissue repair and regeneration. Fuchs et al. (p. 286, published online 20 June) found that mice deficient for the proapoptotic Sept4/ARTS gene have elevated numbers of apoptosis-resistant hair follicle SCs and display dramatic improvement in wound healing and regeneration. Inactivation of the caspase inhibitor XIAP, a direct target for the proapoptotic activity of ARTS, abrogated these phenotypes and impaired wound healing.

Abstract

Adult stem cells are essential for tissue homeostasis and wound repair. Their proliferative capacity must be tightly regulated to prevent the emergence of unwanted and potentially dangerous cells, such as cancer cells. We found that mice deficient for the proapoptotic Sept4/ARTS gene have elevated numbers of hair follicle stem cells (HFSCs) that are protected against apoptosis. Sept4/ARTS−/− mice display marked improvement in wound healing and regeneration of hair follicles. These phenotypes depend on HFSCs, as indicated by lineage tracing. Inactivation of XIAP, a direct target of ARTS, abrogated these phenotypes and impaired wound healing. Our results indicate that apoptosis plays an important role in regulating stem cell–dependent regeneration and suggest that this pathway may be a target for regenerative medicine.

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