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1 Department of Medicine, Columbia University, New York 10032; and 2 Department of Physiology, Cornell University, New York, New York 10021
Renal
epithelial cells derive from either cells of the metanephric mesenchyme
or ureteric bud cells, but the origin of other renal cells is unclear.
To test whether metanephric mesenchymal cells generate cells other than
epithelial, we examined the developmental potential of a metanephric
mesenchymal cell line (7.1.1 cells) and of primary cultures of
metanephric mesenchymal cells. 7.1.1 Cells express both
mesenchymal and epithelial markers and, on confluence, form
well-defined monolayers expressing epithelial junctional proteins.
However, 7.1.1 cells as well as primary cultures of metanephric
mesenchymal cells also generate spindle-shaped cells that are positive
for
-smooth muscle actin, indicating that they are myofibroblasts
and/or smooth muscle; this differentiation pathway is inhibited by
collagen IV and enhanced by fetal calf serum or transforming growth
factor-
1. Transforming growth factor-
1 also induces expression of smooth muscle proteins, indicating that the
cells differentiate into smooth muscle. 7.1.1 Cells as well as primary
cultures of metanephric mesenchymal cells also express vascular
endothelial growth factor receptor 2 and Tie-2, suggesting that the
metanephric mesenchymal cells that generate epithelia may also
differentiate into endothelial cells. The pluripotency of the 7.1.1 cells is self-renewing. The data suggest that the metanephric
mesenchyme contains embryonic renal stem cells.
nephrogenesis; cell differentiation; myofibroblast; transforming
growth factor-
; collagen IV
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