Capturing and profiling adult hair follicle stem cells

被引:1000
作者
Morris, RJ
Liu, YP
Marles, L
Yang, ZX
Trempus, C
Li, SL
Lin, JS
Sawicki, JA
Cotsarelis, G [1 ]
机构
[1] Univ Penn, Sch Med, Dept Dermatol, Kligman Labs, Philadelphia, PA 19104 USA
[2] Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
[4] NIEHS, Canc Biol Grp, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA
[5] Lankenau Inst Med Res, Wynnewood, PA 19096 USA
关键词
D O I
10.1038/nbt950
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:411 / 417
页数:7
相关论文
共 46 条
[31]   A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning [J].
Petiot, A ;
Conti, FJA ;
Grose, R ;
Revest, JM ;
Hodivala-Dilke, KM ;
Dickson, C .
DEVELOPMENT, 2003, 130 (22) :5493-5501
[32]   Keratinocyte stem cells: a commentary [J].
Potten, CS ;
Booth, C .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 119 (04) :888-899
[33]   Stemness: Transcriptional profiling of embryonic and adult stem cells [J].
Ramalho-Santos, M ;
Yoon, S ;
Matsuzaki, Y ;
Mulligan, RC ;
Melton, DA .
SCIENCE, 2002, 298 (5593) :597-600
[34]   FUNCTIONAL-CHARACTERIZATION OF INDIVIDUAL HUMAN HEMATOPOIETIC STEM-CELLS CULTURED AT LIMITING DILUTION ON SUPPORTIVE MARROW STROMAL LAYERS [J].
SUTHERLAND, HJ ;
LANSDORP, PM ;
HENKELMAN, DH ;
EAVES, AC ;
EAVES, CJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (09) :3584-3588
[35]   Involvement of follicular stem cells in forming not only the follicle but also the epidermis [J].
Taylor, G ;
Lehrer, MS ;
Jensen, PJ ;
Sun, TT ;
Lavker, RM .
CELL, 2000, 102 (04) :451-461
[36]   Enrichment for living murine keratinocytes from the hair follicle bulge with the cell surface marker CD34 [J].
Trempus, CS ;
Morris, RJ ;
Bortner, CD ;
Cotsarelis, G ;
Faircloth, RS ;
Reece, JM ;
Tennant, RW .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2003, 120 (04) :501-511
[37]   Reconstruction of damaged corneas by transplantation of autologous limbal epithelial cells. [J].
Tsai, RJ ;
Li, LM ;
Chen, JK .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (02) :86-93
[38]   ASSOCIATION OF BASONUCLIN WITH ABILITY OF KERATINOCYTES TO MULTIPLY AND WITH ABSENCE OF TERMINAL DIFFERENTIATION [J].
TSENG, H ;
GREEN, H .
JOURNAL OF CELL BIOLOGY, 1994, 126 (02) :495-506
[39]   Defining the epithelial stem cell niche in skin [J].
Tumbar, T ;
Guasch, G ;
Greco, V ;
Blanpain, C ;
Lowry, WE ;
Rendl, M ;
Fuchs, E .
SCIENCE, 2004, 303 (5656) :359-363
[40]   Transient activation of β-catenin signaling in cutaneous keratinocytes is to trigger the active growth phase of the hair cycle in mice [J].
Van Mater, D ;
Kolligs, FT ;
Dlugosz, AA ;
Fearon, ER .
GENES & DEVELOPMENT, 2003, 17 (10) :1219-1224