Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth
Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth
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DOI：
10.1073/pnas.1309970110
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发表时间：
2013-12-03
影响因子：
11.1
通讯作者：
Christiano, Angela M.
中科院分区：
文献类型：
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作者：
Higgins, Claire A.;Chen, James C.;Christiano, Angela M.
在一些低等生物和啮齿动物中观察到了新生器官再生；然而，在人类细胞和组织中证明这些再生特性是具有挑战性的。在毛囊中，啮齿动物毛囊来源的真皮细胞可以与局部上皮细胞相互作用，并在各种无毛受体皮肤部位诱导新生毛囊。然而，在人类皮肤中使用人毛乳头细胞来重述这一过程的多次尝试都失败了，这表明人的毛乳头细胞在培养时失去了关键的诱导特性。在这里，我们对培养中的人毛乳头细胞进行了全球基因表达分析，发现非常快速和深刻的分子特征变化将它们从3D环境过渡到2D环境与早期失去诱导毛发的能力联系在一起。我们证明，完整的真皮乳头转录签名可以通过在3D椭圆形培养中生长乳头细胞来部分恢复。这一标志性的变化转化为诱导能力的部分恢复，我们表明，当人毛乳头细胞培养成球状时，能够在人皮肤中诱导新生毛囊。
De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin.