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
[1]   Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development [J].
Andl, T ;
Ahn, K ;
Kairo, A ;
Chu, EY ;
Wine-Lee, L ;
Reddy, ST ;
Croft, NJ ;
Cebra-Thomas, JA ;
Metzger, D ;
Chambon, P ;
Lyons, KM ;
Mishina, Y ;
Seykora, JT ;
Crenshaw, EB ;
Millar, SE .
DEVELOPMENT, 2004, 131 (10) :2257-2268
[2]   Stem cell depletion through epidermal deletion of Rac1 [J].
Benitah, SA ;
Frye, M ;
Glogauer, M ;
Watt, FM .
SCIENCE, 2005, 309 (5736) :933-935
[3]   IDENTIFICATION AND BEHAVIOR OF LABEL-RETAINING CELLS IN ORAL-MUCOSA AND SKIN [J].
BICKENBACH, JR .
JOURNAL OF DENTAL RESEARCH, 1981, 60 :1611-1620
[4]   RATE OF LOSS OF TRITIATED-THYMIDINE LABEL IN BASAL CELLS IN MOUSE EPITHELIAL TISSUES [J].
BICKENBACH, JR ;
MCCUTECHEON, J ;
MACKENZIE, IC .
CELL AND TISSUE KINETICS, 1986, 19 (03) :325-333
[5]   Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche [J].
Blanpain, C ;
Lowry, WE ;
Geoghegan, A ;
Polak, L ;
Fuchs, E .
CELL, 2004, 118 (05) :635-648
[6]   Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis [J].
Braun, KM ;
Niemann, C ;
Jensen, UB ;
Sundberg, JP ;
Silva-Vargas, V ;
Watt, FM .
DEVELOPMENT, 2003, 130 (21) :5241-5255
[7]   Rac1 is crucial for hair follicle integrity but is not essential for maintenance of the epidermis [J].
Chrostek, Anna ;
Wu, Xunwei ;
Quondamatteo, Fabio ;
Hu, Rong ;
Sanecka, Anna ;
Niemann, Catherin ;
Langbein, Lutz ;
Haase, Ingo ;
Brakebusch, Cord .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (18) :6957-6970
[8]   THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY [J].
COSO, OA ;
CHIARIELLO, M ;
YU, JC ;
TERAMOTO, H ;
CRESPO, P ;
XU, NG ;
MIKI, T ;
GUTKIND, JS .
CELL, 1995, 81 (07) :1137-1146
[9]   LABEL-RETAINING CELLS RESIDE IN THE BULGE AREA OF PILOSEBACEOUS UNIT - IMPLICATIONS FOR FOLLICULAR STEM-CELLS, HAIR CYCLE, AND SKIN CARCINOGENESIS [J].
COTSARELIS, G ;
SUN, TT ;
LAVKER, RM .
CELL, 1990, 61 (07) :1329-1337
[10]   Towards a molecular understanding of hair loss and its treatment [J].
Cotsarelis, G ;
Millar, SE .
TRENDS IN MOLECULAR MEDICINE, 2001, 7 (07) :293-301