Development and Homeostasis of the Skin Epidermis
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The first functional characteristic of bulge SCs was their relative quiescence (Cotsarelis et al. 1990). Nucleotide analog pulse-chase experiments showed the presence of label-retaining cells (Bickenbach 1981) in the bulge region of the HF (Cotsarelis et al. 1990), indicating that bulge cells are more quiescent than the other epidermal cells. HF lineage-tracing experiments using tetracycline-regulated green fluorescent protein (GFP)-tagged histone H2B (Tet-o-H2B-GFP) (Tumbar et al. 2004) or the expression of reporter genes under the control of HF-specific promoters such as K15 (Morris et al. 2004), Lgr5 (Jaks et al. 2008), or K19 (Youssef et al. 2010) showed that the cells residing in the bulge and upper germ are responsible for HF regeneration during adult homeostasis. Bulge SCs isolated by microdissection (Rochat et al. 1994; Oshima et al. 2001) or by flow cytometry based on the expression of CD34 (Trempus et al. 2003; Blanpain et al. 2004) or K15-GFP (Morris et al. 2004) and cultured in vitro produced large proliferative colonies that could be propagated for a long time. Transplantation of the progeny of a single bulge SC can generate all HF lineages (Blanpain et al. 2004; Claudinot et al. 2005). During anagen, bulge SCs migrate along the ORS to the matrix, where they proliferate, differentiate, and produce the inner root sheath (IRS) and the hair shaft (Oshima et al. 2001; Ito et al. 2004; Tumbar et al. 2004).