Deciphering the cellular and molecular landscapes of Wnt/β-catenin signaling in mouse embryonic kidney development

Background: The Wnt/beta-catenin signaling pathway is critical in kidney development, yet its specific effects on gene expression in different embryonic kidney cell types are not fully understood. Methods: Wnt/beta-catenin signaling was activated in mouse E12.5 kidneys in vitro using CHIR99021, with RNA sequencing performed afterward, and the results were compared to DMSO controls (dataset GSE131240). Differential gene expression in ureteric buds and cap mesenchyme following pathway activation (datasets GSE20325 and GSE39583) was analyzed. Single-cell RNA-seq data from the Mouse Cell Atlas was used to link differentially expressed genes (DEGs) with kidney cell types. beta-catenin ChIP-seq data (GSE39837) identified direct transcriptional targets. Results: Activation of Wnt/beta-catenin signaling led to 917 significant DEGs, including the upregulation of Notum and Apcdd1 and the downregulation of Crym and Six2. These DEGs were involved in kidney development and immune response. Single-cell analysis identified 787 DEGs across nineteen cell subtypes, with Macrophage_Apoe high cells showing the most pronounced enrichment of Wnt/beta-catenin-activated genes. Gene expression profiles in ureteric buds and cap mesenchyme differed significantly upon beta-catenin manipulation, with cap mesenchyme showing a unique set of DEGs. Analysis of beta-catenin ChIP-seq data revealed 221 potential direct targets, including Dpp6 and Fgf12. Conclusion: This study maps the complex gene expression driven by Wnt/beta-catenin signaling in embryonic kidney cell types. The identified DEGs and beta-catenin targets elucidate the molecular details of kidney development and the pathway's role in immune processes, providing a foundation for further research into Wnt/beta-catenin signaling in kidney development and disease.