Diversity, Topographic Differentiation, and Positional Memory in Human Fibroblasts

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. Notablegroups of differentially expressed genes included some implicated in extracellular matrixsynthesis, lipid metabolism, and cell signaling pathways that control proliferation, cellmigration, and fate determination. Several genes implicated in genetic diseases werefound to be expressed in fibroblasts in an anatomic pattern that paralleled the phenotypicdefects. Finally, adult fibroblasts maintained key features of Hox gene expressionpatterns established during embryogenesis, suggesting that Hox genes may directtopographic differentiation and underlie the detailed positional memory in fibroblasts. Keywords: Logical Set