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Capturing and profiling adult hair follicle stem cells

Abstract

The hair follicle bulge possesses putative epithelial stem cells. Characterization of these cells has been hampered by the inability to target bulge cells genetically. Here, we use a Keratin1-15 (Krt1-15, also known as K15) promoter to target mouse bulge cells with an inducible Cre recombinase construct or with the gene encoding enhanced green fluorescent protein (EGFP), which allow for lineage analysis and for isolation of the cells. We show that bulge cells in adult mice generate all epithelial cell types within the intact follicle and hair during normal hair follicle cycling. After isolation, adult Krt1-15-EGFP-positive cells reconstituted all components of the cutaneous epithelium and had a higher proliferative potential than Krt1-15-EGFP-negative cells. Genetic profiling of hair follicle stem cells revealed several known and unknown receptors and signaling pathways important for maintaining the stem cell phenotype. Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair.

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Figure 1: All keratinocyte lineages within hair follicles are derived from bulge cells during normal hair follicle cycling in vivo.
Figure 2: Isolation of hair follicle bulge cells from dorsal skin of adult Krt-15-EGFP mice.
Figure 3: Isolated hair follicle bulge cells exhibit a high proliferative potential in vitro and retain their pluripotent nature.

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Acknowledgements

We thank Jean Richa for generation of transgenic mice, Hank Pletcher for assistance with FACS, Don Baldwin for microarray analysis, Dorothy Campbell for histological preparations and John Stanley and Peter Sterling for discussion and comments on the manuscript. This work was supported by NIH grants AR46837 to G.C. and CA97957 to R.J.M. and G.C.

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Correspondence to George Cotsarelis.

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Morris, R., Liu, Y., Marles, L. et al. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 22, 411–417 (2004). https://doi.org/10.1038/nbt950

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