Centre d'Etude des Cellules Souches, I-Stem, Association Française Contre les Myopathies, 91030 Evry cedex, France.
Proc Natl Acad Sci U S A. 2011 Sep 6;108(36):14861-6. doi: 10.1073/pnas.1019070108. Epub 2011 Aug 19.
Melanocytes are essential for skin homeostasis and protection, and their defects in humans lead to a wide array of diseases that are potentially extremely severe. To date, the analysis of molecular mechanisms and the function of human melanocytes have been limited because of the difficulties in accessing large numbers of cells with the specific phenotypes. This issue can now be addressed via a differentiation protocol that allows melanocytes to be obtained from pluripotent stem cell lines, either induced or of embryonic origin, based on the use of moderate concentrations of a single cytokine, bone morphogenic protein 4. Human melanocytes derived from pluripotent stem cells exhibit all the characteristic features of their adult counterparts. This includes the enzymatic machinery required for the production and functional delivery of melanin to keratinocytes. Melanocytes also integrate appropriately into organotypic epidermis reconstructed in vitro. The availability of human cells committed to the melanocytic lineage in vitro will enable the investigation of those mechanisms that guide the developmental processes and will facilitate analysis of the molecular mechanisms responsible for genetic diseases. Access to an unlimited resource may also prove a vital tool for the treatment of hypopigmentation disorders when donors with matching haplotypes become available in clinically relevant banks of pluripotent stem cell lines.
黑素细胞对于皮肤的稳态和保护至关重要，其在人类中的缺陷会导致多种潜在的严重疾病。迄今为止，由于难以获得具有特定表型的大量细胞，对人类黑素细胞的分子机制和功能的分析一直受到限制。现在，通过一种分化方案，可以解决这个问题，该方案基于使用中等浓度的单一细胞因子骨形态发生蛋白 4，从多能干细胞系（无论是诱导的还是胚胎来源的）中获得黑素细胞。源自多能干细胞的人类黑素细胞表现出与成体黑素细胞完全相同的特征。这包括用于黑色素向角质形成细胞生产和功能传递所需的酶机制。黑素细胞也适当地整合到体外重建的器官型表皮中。体外定向为黑素细胞系的人类细胞的可用性将能够研究指导发育过程的机制，并有助于分析负责遗传疾病的分子机制。当具有匹配单倍型的供体可用于临床相关的多能干细胞系库时，获得无限量的资源也可能成为治疗色素减退性疾病的重要工具。
