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                <term xml:lang="en">Kidney regeneration</term>
                <term xml:lang="en">catshark</term>
                <term xml:lang="en">nephron progenitor cells</term>
                <term xml:lang="en">translational control</term>
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              <p>Key PointsUnlike mammals, chondrichthyan species exhibit postembryonic nephrogenesis, where new nephrons are continuously added in the kidney. Nephron progenitor cells in catsharks display slow cycling property, akin to other somatic stem cells, indicating their potential for tissue renewal and regeneration. Molecular analysis suggests a potential link between protein synthesis rate and nephron progenitor cell maintenance. Background While adult mammals are unable to grow new nephrons, cartilaginous fish kidneys display nephrogenesis throughout life. In this study, we investigated the molecular properties of nephron progenitor cells (NPCs) within the kidney of the catshark ( Scyliorhinus canicula ). Methods We used branched DNA in situ hybridization to analyze markers expressed in catshark NPCs. Bromodesoxyuridine pulse-chase labeling was also performed to test whether NPCs are slow-cycling cells. To question the mechanisms allowing NPC maintenance in the catshark postembryonic kidney, we measured global protein synthesis rates using in vivo OP-puromycin incorporation. We also investigated the expression of two targets of the mammalian target of rapamycin pathway, an important signaling pathway for translation initiation. Results We found that NPCs express molecular markers previously identified in mice and teleost embryonic NPCs, such as the transcription factors Six2, Pax2, and Wt1. At postembryonic stages, these NPCs are integrated into a specific nephrogenic area of the kidney and contain slow-cycling cells. We also evidenced that NPCs have lower protein synthesis levels than the differentiated cells present in forming nephrons. Such transition from low to high translation rates has been previously observed in several populations of vertebrate stem cells as they undergo differentiation. Finally, we reported the phosphorylation of two targets of the mammalian target of rapamycin pathway, p4E-BP1 and pS6K1, in catshark differentiated epithelial cells but not in the NPCs. Conclusions This first molecular analysis of NPCs in a chondrichthyan species indicates that translation rate increases in NPCs as they differentiate into epithelial cells of the nephron.</p>
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