Mechanisms of hair graying: Incomplete melanocyte stem cell maintenance in the niche

被引：538

作者：

Nishimura, EK

Granter, SR

Fisher, DE

机构：

[1] Harvard Univ, Sch Med, Boston Childrens Hosp,Dana Farber Canc Inst, Dept Pediat Hematol Oncol,Melanoma Program Med On, Boston, MA 02115 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA

来源：

SCIENCE | 2005年 / 307卷 / 5710期

关键词：

D O I：

10.1126/science.1099593

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells. This process is accelerated dramatically with Bcl2 deficiency, which causes selective apoptosis of melanocyte stem cells, but not of differentiated melanocytes, within the niche at their entry into the dormant state. Furthermore, physiologic aging of melanocyte stem cells was associated with ectopic pigmentation or differentiation within the niche, a process accelerated by mutation of the melanocyte master transcriptional regulator Mitf.

引用

页码：720 / 724

页数：5

共 31 条

[1] Human hair greying is linked to a specific depletion of hair follicle melanocytes affecting both the bulb and the outer root sheath [J].

Commo, S ;

Gaillard, O ;

Bernard, BA .

BRITISH JOURNAL OF DERMATOLOGY, 2004, 150 (03) :435-443

[2] Melanocyte subpopulation turnover during the human hair cycle: An immunohistochemical study [J].

Commo, S ;

Bernard, BA .

PIGMENT CELL RESEARCH, 2000, 13 (04) :253-259

[3] Premature aging in mice deficient in DNA repair and transcription [J].

de Boer, J ;

Andressoo, JO ;

de Wit, J ;

Huijmans, J ;

Beems, RB ;

van Steeg, H ;

Weeda, G ;

van der Horst, GTJ ;

van Leeuwen, W ;

Themmen, APN ;

Meradji, M ;

Hoeijmakers, JHJ .

SCIENCE, 2002, 296 (5571) :1276-1279

[4] The role of apoptosis in the regulation of hematopoietic stem cells:: Overexpression of BCL-2 increases both their number and repopulation potential [J].

Domen, J ;

Cheshier, SH ;

Weissman, IL .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (02) :253-263

[5] MLANA/MART1 and SlLV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma [J].

Du, JY ;

Miller, AJ ;

Widlund, HR ;

Horstmann, MA ;

Ramaswamy, S ;

Fisher, DE .

AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (01) :333-343

[6] Genetics of dark skin in mice [J].

Fitch, KR ;

McGowan, KA ;

van Raamsdonk, CD ;

Fuchs, H ;

Lee, D ;

Puech, A ;

Hérault, Y ;

Threadgill, DW ;

de Angelis, MH ;

Barsh, GS .

GENES & DEVELOPMENT, 2003, 17 (02) :214-228

[7] At the roots of a never-ending cycle [J].

Fuchs, E ;

Merrill, BJ ;

Jamora, C ;

DasGupta, R .

DEVELOPMENTAL CELL, 2001, 1 (01) :13-25

[8] DOPA-negative melanocytes in the outer root sheath of human hair follicles express premelanosomal antigens but not a melanosomal antigen or the melanosome-associated glycoproteins tyrosinase, TRP-1, and TRP-2 [J].

Horikawa, T ;

Norris, DA ;

Johnson, TW ;

Zekman, T ;

Dunscomb, N ;

Bennion, SD ;

Jackson, RL ;

Morelli, JG .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1996, 106 (01) :28-35

[9] LIGHT IS A DOMINANT MOUSE MUTATION RESULTING IN PREMATURE CELL-DEATH [J].

JOHNSON, R ;

JACKSON, IJ .

NATURE GENETICS, 1992, 1 (03) :226-229

[10] A MOUSE MODEL FOR VITILIGO [J].

LERNER, AB ;

SHIOHARA, T ;

BOISSY, RE ;

JACOBSON, KA ;

LAMOREUX, ML ;

MOELLMANN, GE .

JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1986, 87 (03) :299-304

← 1 2 3 4 →