Analyses of regenerative wave patterns in adult hair follicle populations reveal macro-environmental regulation of stem cell activity
Analyses of regenerative wave patterns in adult hair follicle populations reveal macro-environmental regulation of stem cell activity
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DOI：
10.1387/ijdb.072564mp
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发表时间：
2009-01-01
影响因子：
0.7
通讯作者：
Chuong, Cheng-Ming
中科院分区：
文献类型：
--
作者：
Plikus, Maksim V.;Widelitz, Randall B.;Chuong, Cheng-Ming
成年哺乳动物皮毛中毛发生长的控制是一个迷人的话题，刚刚开始用分子遗传学工具进行探索。复杂的毛发周期结构域和再生的毛发波浪存在于正常成年（> 2个月）小鼠中，但在具有周期性脱发表型的突变体中更明显。每个毛发周期域由起始位点、传播波和边界组成。通过对毛发生长动态、拔毛后再生所需时间、原位杂交和报告基因活性的分析，我们发现毛囊内Wnt信号存在与毛发周期同步的振荡，真皮骨形态发生蛋白（BMP）信号存在与毛发周期异步的振荡。这两种节律的相互作用导致在休止期识别不应期和主管期，在生长期识别自主期和繁殖期。当生长期波传播到达处于不应期的卵泡时形成边界。实验表明，Krt 14-Nog小鼠具有缩短的不应期和简化的波动动力学。Krt 14-Nog皮肤移植物表现出与周围宿主皮肤的非自主相互作用。将BMP包被的珠粒植入感受态休止期皮肤中可防止珠粒周围的毛发波传播。因此，我们已经开发了一个新的分子理解的经典早期概念的抑制性“抑素”，这表明干细胞在毛囊微环境，或其他器官，受到更高水平的宏观环境调节。这种新的理解在再生医学领域具有重要意义。与皮下脂肪细胞中Bmp 2表达的意外联系对系统生物学和Evo-Devo有影响。
The control of hair growth in the adult mammalian coat is a fascinating topic which has just begun to be explored with molecular genetic tools. Complex hair cycle domains and regenerative hair waves are present in normal adult (> 2 month) mice, but more apparent in mutants with cyclic alopecia phenotypes. Each hair cycle domain consists of initiation site(s), a propagating wave and boundaries. By analyzing the dynamics of hair growth, time required for regeneration after plucking, in situ hybridization and reporter activity, we showed that there is oscillation of intra-follicular Wnt signaling which is synchronous with hair cycling, and there is oscillation of dermal bone morphogenetic protein (BMP) signaling which is asynchronous with hair cycling. The interactions of these two rhythms lead to the recognition of refractory and competent phases in the telogen, and autonomous and propagating phases in the anagen. Boundaries form when propagating anagen waves reach follicles which are in refractory telogen. Experiments showed that Krt14-Nog mice have shortened refractory telogen and simplified wave dynamics. Krt14-Nog skin grafts exhibit non-autonomous interactions with surrounding host skin. Implantation of BMP coated beads into competent telogen skin prevents hair wave propagation around the bead. Thus, we have developed a new molecular understanding of the classic early concepts of inhibitory "chalone", suggesting that stem cells within the hair follicle micro-environment, or other organs, are subject to a higher level of macro-environmental regulation. Such a novel understanding has important implications in the field of regenerative medicine. The unexpected links with Bmp2 expression in subcutaneous adipocytes has implications for systems biology and Evo-Devo.