Epidermal Wnt/β-catenin signaling regulates adipocyte differentiation via secretion of adipogenic factors

被引:132
作者
Donati, Giacomo [1 ,2 ]
Proserpio, Valentina [3 ]
Lichtenberger, Beate Maria [1 ]
Natsuga, Ken [2 ,4 ]
Sinclair, Rodney [5 ,6 ]
Fujiwara, Hironobu [2 ,7 ]
Watt, Fiona M. [1 ]
机构
[1] Kings Coll London, Ctr Stem Cells & Regenerat Med, London SE1 9RT, England
[2] Canc Res UK Cambridge Res Inst, Cambridge CB2 0RE, England
[3] Wellcome Trust Sanger Inst, European Bioinformat Inst, Hinxton CB10 1SD, England
[4] Hokkaido Univ, Grad Sch Med, Dept Dermatol, Sapporo, Hokkaido 0608638, Japan
[5] Univ Melbourne, Melbourne, Vic, Australia
[6] Epworth Med Fdn, Melbourne, Vic, Australia
[7] RIKEN Ctr Dev Biol, Lab Tissue Microenvironm, Kobe, Hyogo 6500047, Japan
基金
英国惠康基金; 英国医学研究理事会;
关键词
skin; niche cross-talk; stem cells; HAIR FOLLICLE MORPHOGENESIS; ADULT-MOUSE EPIDERMIS; ADIPOSE CELL LINE; BETA-CATENIN; STEM-CELLS; IN-VIVO; SKIN; ACTIVATION; TUMORS; PROLIFERATION;
D O I
10.1073/pnas.1312880111
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
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
It has long been recognized that the hair follicle growth cycle and oscillation in the thickness of the underlying adipocyte layer are synchronized. Although factors secreted by adipocytes are known to regulate the hair growth cycle, it is unclear whether the epidermis can regulate adipogenesis. We show that inhibition of epidermal Wnt/beta-catenin signaling reduced adipocyte differentiation in developing and adult mouse dermis. Conversely, ectopic activation of epidermal Wnt signaling promoted adipocyte differentiation and hair growth. When the Wnt pathway was activated in the embryonic epidermis, there was a dramatic and premature increase in adipocytes in the absence of hair follicle formation, demonstrating that Wnt activation, rather than mature hair follicles, is required for adipocyte generation. Epidermal and dermal gene expression profiling identified keratinocyte-derived adipogenic factors that are induced by beta-catenin activation. Wnt/beta-catenin signaling-dependent secreted factors from keratinocytes promoted adipocyte differentiation in vitro, and we identified ligands for the bone morphogenetic protein and insulin pathways as proadipogenic factors. Our results indicate epidermal Wnt/beta-catenin as a critical initiator of a signaling cascade that induces adipogenesis and highlight the role of epidermal Wnt signaling in synchronizing adipocyte differentiation with the hair growth cycle.
引用
收藏
页码:E1501 / E1509
页数:9
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