Integrating spatial transcriptomics with single-cell transcriptomics reveals a spatiotemporal gene landscape of the...

Area of Science:

• Developmental Biology
• Genomics
• Organoid Technology

Background:

• Understanding the spatiotemporal gene landscape is crucial for insights into human kidney development.
• This knowledge aids in the cultivation of kidney organoids.
• The study focuses on human embryonic kidneys at 9 and 18 post-conception weeks (PCW).

Purpose of the Study:

• To profile the spatiotemporal gene programs in developing human kidneys.
• To integrate spatial and single-cell transcriptomics for detailed analysis.
• To elucidate gene characteristics and regulatory networks in kidney development.

Main Methods:

• Microarray-based spatial transcriptomics
• Single-cell transcriptomics (scRNA-seq)
• Cell-type deconvolution and multimodal intersection analyses
• Weighted gene co-expression network analysis

Main Results:

• Mapped transcriptomic signatures of cell types onto spatial kidney sections.
• Identified gene characteristics in medullary regions, noting high mitochondrial activity and glycolysis.
• Established a GDNF-ETV4 centered regulatory network for nephrogenic niche development.
• Highlighted the roles of Wnt, FGF, and JAG1-Notch2 signaling in renal branching morphogenesis.

Conclusions:

• The spatiotemporal gene program provides a detailed map of developing human kidneys.
• Findings are expected to enhance the understanding of kidney development.
• This research supports advancements in kidney organoid development and regenerative medicine.