A Synthetic Niche for Nephron Progenitor Cells

• DOI: 10.1016/j.devcel.2015.06.021
• Publication Date: 2015-07-17T05:28:02Z
• Authors: Aaron C. Brown; Sree Deepthi Muth...; Leif Oxburgh
• Keywords: Homeodomain Proteins; Smad5 Protein; 0301 basic medicine; Mice, Inbred ICR; Organogenesis; Nuclear Proteins; Cell Differentiation; Mice, Transgenic; Nephrons; Smad1 Protein; Enzyme Activation; Fibroblast Growth Factors; Mice; 03 medical and health sciences; Pyrimidines; Bone Morphogenetic Proteins; Animals; Pyrazoles; Apoptosis Regulatory Proteins; Cells, Cultured; Embryonic Stem Cells; Developmental Biology; Cell Proliferation

FGF, BMP, and WNT balance embryonic nephron progenitor cell (NPC) renewal and differentiation. By modulating these pathways, we have created an in vitro niche in which NPCs from embryonic kidneys or derived from human embryonic stem cells can be propagated. NPC cultures expanded up to one billion-fold in this environment can be induced to form tubules expressing nephron differentiation markers. Single-cell culture reveals phenotypic variability within the early CITED1-expressing NPC compartment, indicating that it is a mixture of cells with varying progenitor potential. Furthermore, we find that the developmental age of NPCs does not correlate with propagation capacity, indicating that cessation of nephrogenesis is related to factors other than an intrinsic clock. This in vitro nephron progenitor niche will have important applications for expansion of cells for engraftment and will facilitate investigation of mechanisms that determine the balance between renewal and differentiation in these cells.