MP44-09 UNDERSTANDING PRUNE BELLY SYNDROME AT SINGLE CELL RESOLUTION

Area of Science:

• Urology
• Genetics
• Cell Biology

Background:

• Prune Belly Syndrome (PBS) involves bladder dysmyogenesis, leading to a dysfunctional, thick-walled bladder with excess collagen.
• Understanding the cellular and molecular alterations in PBS bladders is crucial for developing effective treatments.

Purpose of the Study:

• To dissect the cellular heterogeneity and gene expression networks altered in Prune Belly Syndrome (PBS) human bladders.
• To identify potential diagnostic markers and therapeutic targets for PBS.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on bladder tissue from 2 PBS patients and 6 controls.
• Cell type clusters were identified using Uniform Manifold Approximation and Projection (UMAP), and differentially expressed genes (DEGs) were analyzed.
• Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted on PBS-affected genes.

Main Results:

• Identified 17 distinct bladder cell clusters, including fibroblasts, smooth muscle (SM), and urothelial cells.
• PBS bladders showed significant fibroblast enrichment (67% vs 40% in controls) and dramatic reductions in SM (5% vs 11%) and urothelial (<1% vs 7%) populations.
• PBS fibroblasts were enriched in collagen genes, and both fibroblast and SM cells exhibited pathways associated with neurodegenerative diseases.

Conclusions:

• scRNA-seq revealed disarrayed cell populations and unique transcriptomic signatures in PBS bladders.
• The identified transcriptomic map highlights similarities between PBS and neurodegenerative diseases.
• This study provides a foundation for developing diagnostic markers and therapeutic interventions for Prune Belly Syndrome.