Kidney, blood, and endothelium: developmental expression of stem cell leukemia during nephrogenesis

In vertebrates the hematopoietic and renal tissues share a common mesodermal origin. Recently, we have analyzed global gene expression during human nephrogenesis and observed up-regulation of stem cell leukemia (SCL), a transcription factor critical for hematopoietic and endothelial lineage specification. Here we characterize the expression of SCL along with its distinct 3' hematopoietic and endothelial enhancer (SCL 3'En) during kidney development.

mRNA and protein expression of SCL were examined in developing murine and human kidneys by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The activity of SCL 3'En was examined by X-galactosidase (X-gal) staining of embryonic kidneys obtained from SCL +6E5/lacZ/3'En transgenic mice and by reporter lacZ assay in various renal cell lines.

We found developmental regulation of SCL mRNA with highest levels of expression in embryonic day 17 (E17) mouse kidneys and lowest in postnatal and adult kidneys. Immunostaining of human fetal kidneys demonstrated the protein predominantly in the nephrogenic cortex and particularly in mesenchymal cells and developing glomeruli. Similarly, SCL +6E5/lacZ/3'En transgenic kidneys showed prominent lacZ staining in cells resembling undifferentiated mesoderm cells in close proximity to S and comma-shaped primitive nephrons and in peritubular and glomerular vessel endothelium. The SCL 3'En was activated in the human embryonic kidney cell line (HEK 293), but not in cell lines derived from adult kidney.

These observations suggest a possible role for SCL in renal vasculogenesis. Undifferentiated mesenchymal cells expressing SCL during early nephrogenesis might represent putative progenitors that can simultaneously give rise to kidney, blood, and endothelium.