Kidney stem cells in development, regeneration and cancer

Area of Science:

• Developmental Biology
• Stem Cell Biology
• Nephrology

Background:

• Nephron generation involves mesenchymal to epithelial transition (MET) of stem cells in the nephrogenic cortex.
• These cells can become oncogenic, leading to pediatric renal cancer.
• The role of adult stem cells in kidney maintenance post-MET is debated.

Purpose of the Study:

• To investigate the model of adult kidney growth and maintenance by stem cells.
• To explore the potential for clonal expansion and self-renewal in differentiated kidney cells.
• To advance renal regenerative medicine by understanding kidney-forming capacities.

Main Methods:

• Genetic lineage tracing of single kidney cells in vivo.
• Analysis of clonal evolution in kidney organoids.
• Observation of Wnt-activated kidney cells to assess clonogenic hierarchy.

Main Results:

• Evidence suggests fate-restricted unipotent clonal expansions drive cell needs, challenging multipotent adult stem cell models.
• Lineage-restriction was observed in cultured kidney organoids.
• Wnt activation in kidney cells demonstrated significant clonal progeny and a clonogenic hierarchy.

Conclusions:

• In vivo nephron epithelia possess a capacity akin to unipotent stem/progenitors, capable of clonal expansion.
• Mature differentiated kidney cells can self-renew and proliferate under specific stimuli.
• Preserving and expanding ex vivo kidney-forming capacity is vital for renal regenerative medicine.