Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline
Dermal papilla cell number specifies hair size, shape and cycling and its reduction causes follicular decline
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DOI：
10.1242/dev.090662
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发表时间：
2013-04-15
期刊：
影响因子：
4.6
通讯作者：
Morgan, Bruce A.
中科院分区：
文献类型：
--
作者：
Chi, Woo;Wu, Eleanor;Morgan, Bruce A.
虽然毛干源自毛囊上皮中角质形成细胞干细胞的后代，但毛囊角质形成细胞的生长和分化是由一种特殊的间充质群体——毛乳头（DP）引导的，毛乳头嵌入在毛球中。在此我们表明，毛囊中毛乳头细胞的数量与小鼠皮毛中产生的毛发的大小和形状相关。同一干细胞库在连续的毛发周期中产生不同大小或类型的毛发，并且这种转变伴随着毛乳头细胞数量的相应变化。利用一种可在体内选择性消融毛乳头细胞的小鼠模型，我们表明毛乳头细胞数量决定毛发的大小和形状。此外，我们证实了毛乳头在激活干细胞以启动新毛干形成中起关键作用这一假说。当毛乳头细胞数量降至临界阈值以下时，具有正常角质形成细胞区室的毛囊无法产生新的毛发。然而，具有稍多毛乳头细胞的邻近毛囊能够重新进入生长期，并且那些进入生长期的毛囊利用一种内在机制来恢复毛乳头细胞数量和正常的毛发生长。这些结果表明间充质微环境指导干细胞和祖细胞的行为以启动再生并决定毛发形态。小鼠毛乳头群体的退化导致在人类衰老过程中观察到的毛发变细和脱落的类型，此处报道的结果提示了逆转脱发的新方法。
Although the hair shaft is derived from the progeny of keratinocyte stem cells in the follicular epithelium, the growth and differentiation of follicular keratinocytes is guided by a specialized mesenchymal population, the dermal papilla (DP), that is embedded in the hair bulb. Here we show that the number of DP cells in the follicle correlates with the size and shape of the hair produced in the mouse pelage. The same stem cell pool gives rise to hairs of different sizes or types in successive hair cycles, and this shift is accompanied by a corresponding change in DP cell number. Using a mouse model that allows selective ablation of DP cells in vivo, we show that DP cell number dictates the size and shape of the hair. Furthermore, we confirm the hypothesis that the DP plays a crucial role in activating stem cells to initiate the formation of a new hair shaft. When DP cell number falls below a critical threshold, hair follicles with a normal keratinocyte compartment fail to generate new hairs. However, neighbouring follicles with a few more DP cells can re-enter the growth phase, and those that do exploit an intrinsic mechanism to restore both DP cell number and normal hair growth. These results demonstrate that the mesenchymal niche directs stem and progenitor cell behaviour to initiate regeneration and specify hair morphology. Degeneration of the DP population in mice leads to the types of hair thinning and loss observed during human aging, and the results reported here suggest novel approaches to reversing hair loss.