Requirement of Rac1 distinguishes follicular from interfollicular epithelial stem cells

被引:48
作者
Castilho, R. M.
Squarize, C. H.
Patel, V.
Millar, S. E.
Zheng, Y.
Molinolo, A.
Gutkind, J. S.
机构
[1] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA
[2] Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
[4] Univ Cincinnati, Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH USA
关键词
epithelial stem cells; hair follicle; Rho GTPases; Rac1; epidermal regeneration;
D O I
10.1038/sj.onc.1210322
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epithelial stem cells in the bulge region within the hair follicle maintain the cyclic hair growth, but whether these stem cells also contribute to the epidermal renewal remains unclear. Here, we observed that the conditional deletion of the Rac1 gene in the mouse skin, including the potential follicular and epidermal stem cell compartments, results in alopecia owing to defective hair development. Surprisingly, mice lacking the expression of this Rho GTPase do not display major alterations in the interfollicular skin. Furthermore, Rac1 excision from primary epithelial keratinocytes results in the inability to reconstitute hair follicles and sebaceous glands when grafted onto mice, but epithelial cells lacking Rac1 can nonetheless form a healthy epidermi s. Together, these findings support the emerging view that the epidermis and the hair follicles are maintained by different epithelial stem cells, and provide evidence that the requirement for Rac1 function can distinguish these distinct stem cells populations.
引用
收藏
页码:5078 / 5085
页数:8
相关论文
共 25 条
[11]   Epithelial stem cells: A folliculocentric view [J].
Cotsarelis, George .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2006, 126 (07) :1459-1468
[12]   Rho GTPases in cell biology [J].
Etienne-Manneville, S ;
Hall, A .
NATURE, 2002, 420 (6916) :629-635
[13]   Getting under the skin of epidermal morphogenesis [J].
Fuchs, E ;
Raghavan, S .
NATURE REVIEWS GENETICS, 2002, 3 (03) :199-209
[14]   Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases [J].
Gu, Y ;
Filippi, MD ;
Cancelas, JA ;
Siefring, JE ;
Williams, EP ;
Jasti, AC ;
Harris, CE ;
Lee, AW ;
Prabhakar, R ;
Atkinson, SJ ;
Kwiatkowski, DJ ;
Williams, DA .
SCIENCE, 2003, 302 (5644) :445-449
[15]   MUSCARINIC ACETYLCHOLINE-RECEPTOR SUBTYPES AS AGONIST-DEPENDENT ONCOGENES [J].
GUTKIND, JS ;
NOVOTNY, EA ;
BRANN, MR ;
ROBBINS, KC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :4703-4707
[16]   Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis [J].
Ito, M ;
Liu, YP ;
Yang, ZX ;
Nguyen, J ;
Liang, F ;
Morris, RJ ;
Cotsarelis, G .
NATURE MEDICINE, 2005, 11 (12) :1351-1354
[17]   Distinct stem cell populations regenerate the follicle and interfollicular epidermis [J].
Levy, V ;
Lindon, C ;
Harfe, BD ;
Morgan, BA .
DEVELOPMENTAL CELL, 2005, 9 (06) :855-861
[18]   IN-VIVO REGULATION OF MURINE HAIR-GROWTH - INSIGHTS FROM GRAFTING DEFINED CELL-POPULATIONS ONTO NUDE-MICE [J].
LICHTI, U ;
WEINBERG, WC ;
GOODMAN, L ;
LEDBETTER, S ;
DOOLEY, T ;
MORGAN, D ;
YUSPA, SH .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1993, 101 (01) :S124-S129
[19]   Molecular mechanisms regulating hair follicle development [J].
Millar, SE .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2002, 118 (02) :216-225
[20]   EVIDENCE THAT THE CENTRALLY AND PERIPHERALLY LOCATED CELLS IN THE MURINE EPIDERMAL PROLIFERATIVE UNIT ARE 2 DISTINCT CELL-POPULATIONS [J].
MORRIS, RJ ;
FISCHER, SM ;
SLAGA, TJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1985, 84 (04) :277-281