Capturing and profiling adult hair follicle stem cells.
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.
Morris
Rebecca J
RJ
Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Liu
Yaping
Y
Marles
Lee
L
Yang
Zaixin
Z
Trempus
Carol
C
Li
Shulan
S
Lin
Jamie S
JS
Sawicki
Janet A
JA
Cotsarelis
George
G
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D019070:Cell Lineage; D002469:Cell Separation; D018076:DNA, Complementary / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology*; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005821:Genetic Techniques; D049452:Green Fluorescent Proteins; D018859:Hair Follicle / Q000378:metabolism / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D045522:Recombinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D014158:Transcription, Genetic; D015854:Up-Regulation
D018076:DNA, Complementary; D008164:Luminescent Proteins; D012333:RNA, Messenger; D045522:Recombinases; D049452:Green Fluorescent Proteins; D012313:RNA