Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development

Area of Science:

• Developmental biology
• Genomics
• Comparative biology

Background:

• The mammalian kidney develops from nephron and ureteric progenitor cells to maintain fluid homeostasis.
• Understanding kidney epithelial network development is crucial for insights into renal function and disease.

Purpose of the Study:

• To compare chromatin organization and gene expression in developing human and mouse kidneys.
• To identify conserved and divergent regulatory programs in kidney development across species.
• To link developmental findings to human kidney diseases.

Main Methods:

• Single-nuclear assay for transposase-accessible chromatin sequencing (ATAC-seq) and single-cell/nuclear RNA sequencing (RNA-seq) were performed on developing human and mouse kidneys.
• Datasets from 10 developing human kidneys (10.6–17.6 weeks) and 10 mouse kidneys (post-natal day 0) were analyzed.
• Cross-species, multimodal datasets were integrated and computationally analyzed to identify conserved and divergent features.

Main Results:

• Comparative analysis revealed conserved and species-specific regulatory programs in kidney development.
• Human-enriched gene activity suggests unique signaling interactions during human kidney development.
• Human-specific enhancer regions were associated with kidney diseases via genome-wide association studies (GWASs).

Conclusions:

• Developmental modeling provides potential clinical insights into kidney diseases.
• Comparative genomics of kidney development highlights species-specific regulatory mechanisms.
• This study establishes a foundation for understanding human-specific kidney development and disease etiology.