Key Roles for Transforming Growth Factor β in Melanocyte Stem Cell Maintenance

被引：203

作者：

Nishimura, Emi K. ^{[1
,2
]}

Suzuki, Misa ^{[2
]}

Igras, Vivien ^{[3
,4
]}

Du, Jinyan ^{[5
,6
]}

Lonning, Scott ^{[7
]}

Miyachi, Yoshiki ^{[8
]}

Roes, Juergen ^{[9
]}

Beermann, Friedrich ^{[10
]}

Fisher, David E. ^{[3
,4
]}

机构：

[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Stem Cell Biol, Chiyoda Ku, Tokyo 1010062, Japan

[2] Kanazawa Univ, Div Stem Cell Med, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan

[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA

[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Melanoma Program Med Oncol, Boston, MA 02114 USA

[5] Broad Inst Biomed Res, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Boston, MA 02115 USA

[7] Genzyme Corp, Cambridge, MA 01701 USA

[8] Kyoto Univ, Grad Sch Med, Dept Dermatol, Sakyo Ku, Kyoto 6068507, Japan

[9] UCL, Windeyer Inst Med Sci, Dept Med, London W1P 6DB, England

[10] Ecole Polytech Fed Lausanne, Sch Life Sci, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland

来源：

CELL STEM CELL | 2010年 / 6卷 / 02期

关键词：

TGF-BETA; IN-VIVO; DOPACHROME TAUTOMERASE; MASTER REGULATOR; SELF-RENEWAL; HAIR CYCLE; NICHE; SKIN; DIFFERENTIATION; ACTIVATION;

D O I：

10.1016/j.stem.2009.12.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Melanocyte stem cells in the bulge area of hair follicles are responsible for hair pigmentation, and defects in them cause hair graying. Here we describe the process of melanocyte stem cell entry into the quiescent state and show that niche-derived transforming growth factor beta (TGF-beta) signaling plays important roles in this process. In vitro, TGF-beta not only induces reversible cell cycle arrest, but also promotes melanocyte immaturity by clownregulating MITF, the master transcriptional regulator of melanocyte differentiation, and its downstream melanogenic genes. In vivo, TGF-beta signaling is activated in melanocyte stem cells when they reenter the quiescent noncycling state during the hair cycle and this process requires Bcl2 for cell survival. Furthermore, targeted TGF-beta type II receptor (TGFbRII) deficiency in the melanocyte lineage causes incomplete maintenance of melanocyte stem cell immaturity and results in mild hair graying. These data demonstrate that the TGF-beta signaling pathway is one of the key niche factors that regulate melanocyte stem cell immaturity and quiescence.

引用

页码：130 / 140

页数：11

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