Axial Nephron Fate Switching Demonstrates a Plastic System Tunable on Demand DOI
MaryAnne Achieng, Jack Schnell,

Connor C. Fausto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

The human nephron is a highly patterned tubular structure. It develops specialized cells that regulate bodily fluid homeostasis, blood pressure, and urine secretion throughout life. Approximately 1 million nephrons form in each kidney during embryonic fetal development, but how they develop poorly understood. Here we interrogate axial patterning mechanisms the using an iPSC-derived organoid system generates hundreds of developmentally synchronized nephrons, compare it to vivo development single cell spatial transcriptomic approaches. We show controlled by integrated WNT/BMP/FGF signaling. Imposing WNT ON /BMP OFF state established distal identity matures into thick ascending loop Henle endogenously activating FGF. Simultaneous suppression FGF signaling switches back proximal cell-state, transformation itself dependent on BMP signal transduction. Our highlights plasticity patterning, delineates roles WNT, FGF, mediated controlling paves way for generating demand.

Language: Английский

Patterning the nephron: Forming an axial polarity with distal and proximal specialization DOI
Nils O. Lindström, Jessica M. Vanslambrouck

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Axial Nephron Fate Switching Demonstrates a Plastic System Tunable on Demand DOI
MaryAnne Achieng, Jack Schnell,

Connor C. Fausto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

The human nephron is a highly patterned tubular structure. It develops specialized cells that regulate bodily fluid homeostasis, blood pressure, and urine secretion throughout life. Approximately 1 million nephrons form in each kidney during embryonic fetal development, but how they develop poorly understood. Here we interrogate axial patterning mechanisms the using an iPSC-derived organoid system generates hundreds of developmentally synchronized nephrons, compare it to vivo development single cell spatial transcriptomic approaches. We show controlled by integrated WNT/BMP/FGF signaling. Imposing WNT ON /BMP OFF state established distal identity matures into thick ascending loop Henle endogenously activating FGF. Simultaneous suppression FGF signaling switches back proximal cell-state, transformation itself dependent on BMP signal transduction. Our highlights plasticity patterning, delineates roles WNT, FGF, mediated controlling paves way for generating demand.

Language: Английский

Citations

0