PUBLICATION

Identification of renal stem cells in zebrafish

Authors
Yu, T., Liu, X., Tan, X., Zhang, Y., He, Z., Yang, W., Tian, T., Li, Y., Zhao, J., Liu, C.
ID
ZDB-PUB-250823-1
Date
2025
Source
Science advances   11: eadx5296eadx5296 (Journal)
Registered Authors
Liu, Chi
Keywords
none
Datasets
GEO:GSE268624
MeSH Terms
  • PAX2 Transcription Factor/genetics
  • PAX2 Transcription Factor/metabolism
  • Stem Cells*/cytology
  • Stem Cells*/metabolism
  • Biomarkers/metabolism
  • Cell Differentiation
  • Nephrons/cytology
  • Nephrons/metabolism
  • Zebrafish*/genetics
  • Wnt Signaling Pathway
  • Intracellular Signaling Peptides and Proteins/genetics
  • Intracellular Signaling Peptides and Proteins/metabolism
  • Animals
  • Single-Cell Analysis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Kidney*/cytology
  • Kidney*/metabolism
  • Cell Proliferation
  • Protein Tyrosine Phosphatases/genetics
  • Protein Tyrosine Phosphatases/metabolism
PubMed
40845090 Full text @ Sci Adv
Abstract
Renal stem cells (RSC) hold great promise as kidney disease regenerative therapies. However, RSCs capable of regenerating de novo nephrons remain unidentified in vertebrates. Therefore, this study aimed to identify RSCs in zebrafish. Single-cell RNA sequencing revealed eya2, pax2a, and six2a as primary markers of zebrafish RSCs. Real-time imaging demonstrated that RSCs originated from eya2-positive mesenchymal cells. Notably, photoconversion-based lineage tracing and serial transplantation assays revealed a unique RSC renewal process, characterized by a differentiation-proliferation-dedifferentiation mode. This process generates nephrons and nascent RSCs concurrently. In addition, precise Wnt signaling is key for RSC renewal and differentiation balance and directly activates eya2 expression to initiate renewal. This discovery establishes a foundation for the advancement of stem cell therapies for kidney diseases.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping