Departments of Dermatology, Genetics and Development, and Systems Biology, Columbia University, New York, NY 10032.
Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19679-88. doi: 10.1073/pnas.1309970110. Epub 2013 Oct 21.
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.
在几种低等生物以及啮齿动物中已经观察到了从头器官再生；然而，在人类细胞和组织中证明这些再生特性一直具有挑战性。在毛囊中，啮齿动物毛囊衍生的真皮细胞可以与局部上皮相互作用，并在各种无毛受体皮肤部位诱导新的毛囊。然而，使用人类皮肤中的人真皮乳头细胞多次尝试在人类中重现这一过程都失败了，这表明人真皮乳头细胞在培养过程中失去了关键的诱导特性。在这里，我们对培养中的人真皮乳头细胞进行了全基因表达分析，发现它们从 3D 环境过渡到 2D 环境的过程中，分子特征发生了非常迅速和深刻的变化，这与它们早期丧失诱导毛发形成的能力有关。我们证明，通过将乳头细胞在 3D 球体培养中生长，可以部分恢复完整的真皮乳头转录特征。这种特征变化转化为诱导能力的部分恢复，我们表明，当作为球体生长时，人真皮乳头细胞能够在人皮肤中诱导新的毛囊。
