Spatial Transcriptomics and Single-Nucleus Multi-Omics Analysis Revealing the Impact of High Maternal Folic Acid...

Area of Science:

• Neuroscience
• Developmental Biology
• Nutritional Science

Background:

• Folate (vitamin B9) is vital for neurogenesis.
• Folic acid (FA) supplementation prevents neural tube defects but excessive intake raises concerns.
• Understanding FA's impact on fetal brain development is crucial.

Purpose of the Study:

• To investigate the effects of high maternal FA supplementation on offspring brain development.
• To identify specific brain regions and cellular mechanisms affected by FA intake.

Main Methods:

• Utilized a mouse model for periconceptional high FA supplementation.
• Employed spatial transcriptomics and single-nucleus multi-omics.
• Analyzed gene expression and chromatin accessibility in offspring brains.

Main Results:

• High maternal FA altered gene pathways for neurogenesis and myelination across brain regions.
• Learning and memory-related gene expression was affected in thalamic and ventricular regions.
• Maturing dentate gyrus (DG) excitatory neurons exhibited aberrant gene expression and chromatin accessibility in ribosomal biogenesis pathways.

Conclusions:

• Maternal high FA supplementation impacts specific brain regions and cell types.
• Aberrant gene expression in DG neurons affects synaptic formation pathways.
• Findings highlight potential risks of excessive FA intake during critical developmental periods.