Understanding how to build a function kidney is a fine balance

Dr Alex Combes and his team are understanding the balance between nephron progenitor cells that commit to forming nephrons or remain in the progenitor pool.

In growing mammalian kidney tissues, there is a balance between the number of nephron progenitor cells that commit to forming nephrons or remain in the progenitor pool. Nephron progenitor commitment is essential for building the functional capacity of the kidney, while uncommitted progenitors drive kidney growth. Understanding this balance is crucial for researchers who are modelling kidney development and disease in the lab.

Nephrons are the functional unit of the kidney; the structure that produces urine in the process of removing waste and excess substances from the blood. There are about 1,000,000 nephrons in each human kidney.

Dr Alex Combes, Team Leader at the Murdoch Children’s Research Institute, Senior Research Fellow at the University of Melbourne and member of the Centre for Stem Cell Systems was the senior author on a recent paper titled ‘Nephron progenitor commitment is a stochastic process influenced by cell migration’, published in eLIFE.

The paper challenges the current idea that nephron progenitor cells commit to turning into nephron cells in a linear fashion. Rather, they observed that cell migration influenced the fate of nephron progenitor cells by allowing them to move away from regionalized signalling cues that trigger nephron formation and instead return to the progenitor pool. This research reveals an unexpected plasticity in nephron progenitor cell fate. The findings were based on time-lapse imaging, as well as computational modelling, and single-cell sequencing.

Dr. Combes previously established new imaging methods to visualise and analyse kidney development, which he has applied with international partners to identify several new genes and signalling pathways as candidate drivers of kidney disease.

This alternative model to explain the balance between nephron progenitor maintenance and commitment may have implications for understanding nephron deficits in kidney tissue, which is a significant risk factor for chronic kidney disease. Dr Combes was recently awarded funding from the National Health and Medical Research Council for further research into how nephron progenitors respond to genetic and environmental cues, which may take Dr Combes and his team a step further towards creating a functional model of kidney tissue in a dish.

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Dr Alex Combes