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Metanephric mesenchyme contains multipotent stem cells whose fate is restricted after induction
D Herzlinger1, C Koseki, T Mikawa
1Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Summary
The mammalian kidney
Area of Science:
- Developmental biology
- Cell biology
- Genetics
Background:
- The mammalian nephron comprises at least fourteen epithelial cell types.
- These diverse cell types originate from the metanephric mesenchyme.
- The cellular composition of the metanephric mesenchyme is not fully understood.
Purpose of the Study:
- To determine if the metanephric mesenchyme contains multipotent stem cells or committed renal cell lines.
- To investigate the differentiation potential of individual renal progenitor cells.
Main Methods:
- Introduction of the lac-Z gene into individual renal progenitors using retroviral-mediated gene transfer.
- Characterization of the differentiated cell types derived from single, lac-Z-tagged metanephric mesenchymal cells after cytodifferentiation.
Main Results:
- The metanephric mesenchyme harbors multipotent stem cells.
- These stem cells can differentiate into at least three distinct epithelial cell types: glomerular, proximal, and distal epithelia.
- The developmental potential of these multipotent cells becomes restricted to a single nephron segment after induction.
Conclusions:
- The metanephric mesenchyme contains multipotent stem cells capable of generating multiple nephron cell lineages.
- Cell fate decisions in renal development involve the restriction of multipotent progenitor potential.
- This study clarifies the cellular origins of nephron diversity.