Diversity, topographic differentiation, and positional memory in human fibroblasts

Abstract

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.

Altered expressions of HOX genes in human cutaneous malignant melanoma

“…In other words, does HOX code function as postal code? Chang et al 29 characterized HOX gene expression patterns in adult human fibroblasts derived from skin at different anatomical sites and found that the fibroblasts showed the site-specific HOX gene expression patterns, suggesting that the fibroblasts maintained key features of HOX gene expression patterns established during embryogenesis. We performed cluster analysis of the 15 melanoma specimens based on the similarity of HOX gene expressions; however, this analysis did not lead to the sorting in accordance with the body sites from which they derived.…”

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

“…MSCs can be harvested from numerous tissues and locations and may have similar surface markers and growth characteristics, however these MSCs display distinct differences [19]. Some studies, including our own published studies [20], suggest that BMMSCs and adipose-derived MSCs (ASCs) are more closely related than to MSCs derived from placental tissues [20,21].…”

Diverse and Specific Gene Expression Responses to Stresses in Cultured Human Cells

“…We saw little or no decrease in the expression of these genes in HeLa cells after the same stresses. About one-half of the genes with specific increases in expression after DTT and menadione treatment in fibroblasts are expressed at a higher level in serum-starved (nondividing) fibroblasts than in fibroblasts grown in the presence of serum (Chang et al, 2002), suggesting that the increased expression of these genes might simply reflect cell cycle arrest. Some of these genes, however, could play an active role in arresting the cell cycle; indeed, several of the genes in this cluster are suspected to regulate proliferation (p53, MAX interacting protein 1, p53-inducible nuclear protein 1, cellular repressor of E1A-stimulated genes, and RB-inhibiting gene 1).…”