Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.

Area of Science:

• Developmental Biology
• Renal Physiology
• Cellular Aging

Background:

• Kidney nephrons originate from mesenchymal progenitors during fetal development.
• Progenitor differentiation and lifespan are critical for kidney formation and function.

Purpose of the Study:

• To investigate intrinsic and extrinsic factors influencing kidney progenitor cell lifespan.
• To understand how aging affects progenitor cell behavior and niche interactions.

Main Methods:

• Utilized a kidney transplantation assay to compare aged and young progenitor engraftment in a young niche.
• Performed single-cell transcriptome profiling to analyze age-dependent molecular changes.
• Assessed progenitor proliferation, niche exit rates, and lifespan post-engraftment.

Main Results:

• Aged progenitors showed decreased proliferation and increased niche exit rates compared to young progenitors.
• Single-cell analysis revealed progressive age-dependent transcriptomic alterations and increased heterogeneity in older populations.
• Elevated mammalian target of rapamycin (mTor) and reduced fibroblast growth factor 20 (Fgf20) were associated with increased exit rates.
• Young neighbors extended the lifespan of aged progenitors by 50% in the niche.

Conclusions:

• Intrinsic aging diminishes kidney progenitor cell proliferation and survival.
• Extrinsic factors, specifically interactions with young progenitor neighbors, can partially rescue aged progenitor lifespan.
• Age-dependent changes in inter-progenitor interactions may drive the cessation of nephrogenesis.