Microarray interrogation of human metanephric mesenchymal cells highlights potentially important molecules in vivo

Many molecules have been implicated in kidney development, often based on experimental animal studies with organ cultures and cell lines. There are very few studies, however, that have directly addressed equivalent living human embryonic tissues. We generated renal mesenchymal cell lines from normal human metanephroi and used a microarray strategy to define changes in gene expression after stimulation with growth factors which enhance nephrogenesis in rodents. Changes were observed in 1) genes modulating diverse general cellular processes, such as matrix metalloproteinase 1 and stanniocalcin 1; 2) genes previously implicated in organogenesis e.g., sprouty 4 and midline 1; and 3) genes involved in blood vessel growth, including angiopoietin 1 and 4. Expression of these same genes was subsequently confirmed in vivo. Our novel data have identified several previously unhighlighted genes that may be implicated in differentiation programs within early human nephrogenesis.