Chang Howard Y, Chi Jen-Tsan, Dudoit Sandrine, Bondre Chanda, van de Rijn Matt, Botstein David, Brown Patrick O
Departments of Dermatology, Biochemistry, Pathology, and Genetics, and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12877-82. doi: 10.1073/pnas.162488599. Epub 2002 Sep 24.
A fundamental feature of the architecture and functional design of vertebrate animals is a stroma, composed of extracellular matrix and mesenchymal cells, which provides a structural scaffold and conduit for blood and lymphatic vessels, nerves, and leukocytes. Reciprocal interactions between mesenchymal and epithelial cells are known to play a critical role in orchestrating the development and morphogenesis of tissues and organs, but the roles played by specific stromal cells in controlling the design and function of tissues remain poorly understood. The principal cells of stromal tissue are called fibroblasts, a catch-all designation that belies their diversity. We characterized genome-wide patterns of gene expression in cultured fetal and adult human fibroblasts derived from skin at different anatomical sites. Fibroblasts from each site displayed distinct and characteristic transcriptional patterns, suggesting that fibroblasts at different locations in the body should be considered distinct differentiated cell types. Notable groups of differentially expressed genes included some implicated in extracellular matrix synthesis, lipid metabolism, and cell signaling pathways that control proliferation, cell migration, and fate determination. Several genes implicated in genetic diseases were found to be expressed in fibroblasts in an anatomic pattern that paralleled the phenotypic defects. Finally, adult fibroblasts maintained key features of HOX gene expression patterns established during embryogenesis, suggesting that HOX genes may direct topographic differentiation and underlie the detailed positional memory in fibroblasts.
脊椎动物的结构和功能设计的一个基本特征是基质，它由细胞外基质和间充质细胞组成，为血管、淋巴管、神经和白细胞提供结构支架和通道。已知间充质细胞和上皮细胞之间的相互作用在组织和器官的发育及形态发生过程中起着关键作用，但特定基质细胞在控制组织设计和功能方面所起的作用仍知之甚少。基质组织的主要细胞被称为成纤维细胞，这个笼统的名称掩盖了它们的多样性。我们对来自不同解剖部位皮肤的培养胎儿和成体人成纤维细胞中的全基因组基因表达模式进行了表征。来自每个部位的成纤维细胞都表现出独特的转录模式，这表明身体不同部位的成纤维细胞应被视为不同的分化细胞类型。显著的差异表达基因群体包括一些与细胞外基质合成、脂质代谢以及控制增殖、细胞迁移和命运决定的细胞信号通路有关的基因。发现一些与遗传疾病相关的基因在成纤维细胞中以与表型缺陷平行的解剖模式表达。最后，成体成纤维细胞维持了胚胎发育过程中建立的HOX基因表达模式的关键特征，这表明HOX基因可能指导地形分化，并构成成纤维细胞中详细位置记忆的基础。
