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The kidney is a complex organ composed of various cell types, each playing a specific role in filtering blood, balancing fluids, and removing waste. These different cell types originate from progenitor cells during development, and the process by which they form and organize is vital to the kidney’s function.
Researchers at the USC School of Medicine conducted an in-depth study comparing the development of kidneys in humans and mice. By examining the chromatin organization (the structure of DNA within cells) and gene expression (how genes are turned on or off), they aimed to understand the similarities and differences in kidney development between these two species.
Chromatin Organization: The researchers used a technique called ATAC-seq (Assay for Transposase-Accessible Chromatin sequencing) to study how DNA is packaged within kidney cells. This method helps identify regions of DNA that are accessible for gene expression.
Gene Expression: They also used single-cell and single-nucleus RNA sequencing (RNA-seq) to analyze which genes are active in individual cells. This method provides a detailed view of the gene activity within the developing kidney.
The study analyzed over 100,000 cells and nuclei from both human and mouse kidneys. The researchers discovered both conserved (shared) and divergent (different) features in chromatin organization and gene expression between the two species.
Species-Specific Insights: One of the major findings was that certain regulatory programs controlling kidney development are unique to humans. These human-specific regulatory elements were linked to kidney diseases, providing potential insights into the genetic basis of these conditions.
Cell Type-Specific Programs: The study also identified specific gene activity and chromatin structures unique to certain kidney cell types. Understanding these differences is important for comprehending how each cell type contributes to the overall function of the kidney.
This research not only enhances our understanding of how kidneys develop but also sheds light on why certain kidney diseases occur. By linking human-specific genetic elements to kidney diseases, the study opens up new avenues for developing targeted therapies.
Additionally, by comparing human and mouse kidney development, researchers can better utilize mouse models in studying human kidney diseases. The findings highlight the importance of considering species-specific differences when using animal models to study human biology.
This study provides a comprehensive look at kidney development in humans and mice, revealing important insights into how our kidneys form and function. By identifying species-specific and cell type-specific regulatory programs, the research enhances our understanding of kidney biology and offers potential pathways for addressing kidney diseases. This knowledge could lead to new diagnostic and therapeutic strategies, ultimately improving kidney health and disease management.
Kim S, Koppitch K, Parvez RK, Guo J, Achieng M, Schnell J, Lindström NO, McMahon AP. (2024) Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development. Dev Cell [Epub ahead of print]. [article]
2024-08-12