Timing is Everything to Build Kidneys From Scratch

Source: University of Southern California

Summary: A team of researchers discovered that arriving early or late can have big consequences for early-stage cells that gather to form a new kidney.

Kidney failure is a leading cause of death for people in the United States. About 662,000 people live on chronic dialysis or with a kidney transplant. Men are 64% more likely than women to suffer end-stage renal disease and the risk for African-Americans is four times higher compared to whites, according to the CDC and the American Kidney Fund.

To achieve the full diversity of cell types in the nephron, when attempting to grow kidneys in laboratory settings, scientists need to understand how these precursor cell types form under normal circumstances in the body. Singlecell RNA sequencing provides a view of all the genes and genetic pathways that are activated when specific cell types form in the nephron. Researchers from the USC showed how progenitor cells that form the kidney’s filtering units, called nephrons, mature into entirely different types of cells based on when they reach the scene of nephron formation. The study findings were published in the journal Developmental Cell.

Filtering unit in kidneys

Developing human nephron, the filtering unit of the kidney. Credit: Nils O. Lindstrom and Tracy Tran/McMahon Lab USC Stem Cell

Specifically, it takes about 1 million nephrons to form a human kidney. The scientists observed that every time one of these structures forms, the nephron progenitor cells (NPCs) gradually commit to becoming various mature cell types and joining the developing nephron. NPCs that arrive early within the nephron start to differentiate and become the “tubule,” which controls the reabsorption of important compounds back into the blood and carries urine away. NPCs that occur late develop into the “glomerulus,” the structure that filters the blood. To show that their predictions were accurate, the team used genetically labeled NPCs in mouse kidneys and grew these under a microscope while capturing images with time-lapse imaging. This allowed them to demonstrate how NPCs gradually move into the newly forming nephron and turn on genes that are specific to particular cell types.

Principal author of the study, Nils O. Lindstrom said, “Timing is critical in determining the type of mature cell that each progenitor will become.”

More Information: Nils O. Lindstrom et al, “Progressive Recruitment of Mesenchymal Progenitors Reveals a Time-Dependent Process of Cell Fate Acquisition in Mouse and Human Nephrogenesis”, Developmental Cell (2018). DOI: https://doi.org/10.1016/j.devcel.2018.05.010

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