BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties
BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties
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DOI：
10.1101/gad.1614408
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发表时间：
2008-02-15
影响因子：
10.5
通讯作者：
Fuchs, Elaine
中科院分区：
文献类型：
--
作者：
Rendl, Michael;Polak, Lisa;Fuchs, Elaine
毛囊(HF)的形成始于上皮干细胞从特化的间充质毛乳头(DP)细胞获得的信号。在培养中，DP细胞失去了诱导HF的特性，但在体内毛发生长过程中，它们驻留在HF球茎内，并指示周围的上皮祖细胞协调复杂的毛发分化程序。为了深入了解维持DP细胞命运的分子程序，我们先前纯化了DP细胞和四个邻近的群体，并定义了它们的细胞类型特定的分子特征。在这里，我们利用这些信息来表明，鳞茎微环境中含有丰富的骨形态发生蛋白(BMPs)，这些蛋白作用于DP细胞，在体外保持关键的特征特征，在体内保持诱导毛发的活性。通过一种新的体外/体内杂交基因敲除实验，我们去除了纯化的DP细胞中的BMP受体1a。当I)Ps不能接收BMP信号时，它们在体外失去特征特征，在体内移植上皮干细胞时不能产生HFs。这些结果表明，BMP信号，除了在上皮干细胞维持和祖细胞分化中的关键作用外，对于DP细胞的功能也是必不可少的，并表明它是形成头发所必需的复杂的上皮-间充质信号的关键特征。
Hair follicle (HF) formation is initiated when epithelial stem cells receive cues from specialized mesenchymal dermal papilla (DP) cells. In culture, DP cells lose their HF-inducing properties, but during hair growth in vivo, they reside within the HF bulb and instruct surrounding epithelial progenitors to orchestrate the complex hair differentiation program. To gain insights into the molecular program that maintains DP cell fate, we previously purified DP cells and four neighboring populations and defined their cell-type-specific molecular signatures. Here, we exploit this information to show that the bulb microenvironment is rich in bone morphogenetic proteins (BMPs) that act on DP cells to maintain key signature features in vitro and hair-inducing activity in vivo. By employing a novel in vitro/in vivo hybrid knockout assay, we ablate BMP receptor la in purified DP cells. When I)Ps cannot receive BMP signals, they lose signature characteristics in vitro and fail to generate HFs when engrafted with epithelial stem cells in vivo. These results reveal that BMP signaling, in addition to its key role in epithelial stem cell maintenance and progenitor cell differentiation, is essential for DP cell function, and suggest that it is a critical feature of the complex epithelial-mesenchymal cross-talk necessary to make hair.