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Published on: February 16, 2017
Deciphering the cellular and molecular landscapes of Wnt/β-catenin signaling in mouse embryonic kidney development
Hui Zhao1, Hui Gong2, Peide Zhu3
1Guangzhou National Laboratory, Guangzhou International Bio Island, No. 9 Xing Dao Huan Bei Road, Guangzhou 510005, Guangdong Province, China.
Background:
The Wnt/β-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/β-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. β-catenin ChIP-seq data (GSE39837) identified direct transcriptional targets.
Results:
Activation of Wnt/β-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/β-catenin-activated genes. Gene expression profiles in ureteric buds and cap mesenchyme differed significantly upon β-catenin manipulation, with cap mesenchyme showing a unique set of DEGs. Analysis of β-catenin ChIP-seq data revealed 221 potential direct targets, including Dpp6 and Fgf12.
Conclusion:
This study maps the complex gene expression driven by Wnt/β-catenin signaling in embryonic kidney cell types. The identified DEGs and β-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/β-catenin signaling in kidney development and disease.
Insights
This study reveals how Wnt/β-catenin signaling impacts gene expression in embryonic kidney cells. It identifies key genes and cell types involved in kidney development and immune responses.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genomics
Background:
- The Wnt/β-catenin signaling pathway is crucial for kidney development.
- Its precise role in regulating gene expression across different embryonic kidney cell types remains unclear.
Purpose of the Study:
- To investigate the effects of Wnt/β-catenin signaling activation on gene expression in embryonic mouse kidneys.
- To identify specific genes and cell types regulated by this pathway during kidney development.
Main Methods:
- Activated Wnt/β-catenin signaling in E12.5 mouse kidneys in vitro using CHIR99021.
- Performed RNA sequencing and analyzed differential gene expression (DEGs) in specific kidney cell populations.
- Utilized single-cell RNA-seq and ChIP-seq data to link DEGs to cell types and identify direct transcriptional targets.
Main Results:
- Identified 917 significant DEGs upon Wnt/β-catenin activation, including notable up- and down-regulations of specific genes.
- Single-cell analysis revealed distinct DEG patterns across 19 cell subtypes, with Macrophage_Apoe high cells showing significant enrichment.
- Found unique gene expression changes in ureteric buds and cap mesenchyme, and identified 221 direct β-catenin targets.
Conclusions:
- This research maps the complex gene expression landscape regulated by Wnt/β-catenin signaling in embryonic kidney cells.
- The findings provide insights into the molecular mechanisms of kidney development and the pathway's involvement in immune processes.
- Establishes a foundation for future studies on Wnt/β-catenin signaling in kidney development and disease.
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