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Axial Nephron Fate Switching Demonstrates a Plastic System Tunable on Demand

GSE283186 Homo sapiens Expression profiling by high throughput sequencing 7 samples Submitted 2025/08/05 Platform GPL34284
Summary
The human nephron is a highly patterned tubular structure. Approximately 1 million nephrons form in each kidney during embryonic and fetal development and develop specialized cells that regulate bodily fluid homeostasis, blood pressure, and urine secretion throughout life. This raises the question of how these cells originally develop. Here we interrogate early human nephron patterning using an iPSC-based kidney organoid system that generates hundreds of developmentally synchronized nephron structures. We show that human nephron patterning is controlled by integrated WNT/BMP/FGF signaling. Imposing a WNThigh/BMPlow state established a distal identity that matures into thick ascending loop of Henle cell identities by activating FGF. Simultaneous suppression of FGF signaling reverts cells to a proximal cell-state, thereby indicating the dependence on FGF signaling for distal cell formation in the human nephron. Our system highlights plasticity in nephron identities and mechanisms controlling normal patterning.
Published in
Axial nephron fate switching demonstrates a plastic system tunable on demand
Achieng MA, Schnell J, Fausto CC et al. · Nature communications 2025 · PMID 40855070 · doi:10.1038/s41467-025-63290-9
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Also filed as BioProject PRJNA1192294 and SRA study SRP548416. Searching any of these in the dataset finder brings you back here.

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