Quantifying Genomic Imprinting at Tissue and Cell Resolution in the Brain

Area of Science:

• Genetics
• Neuroscience
• Epigenetics

Background:

• Genomic imprinting regulates ~150 genes via parental epigenetic marks, crucial for normal brain function.
• Dysregulation of imprinted genes is linked to brain disorders like Prader-Willi and Angelman syndromes.
• Current research relies heavily on mouse models, necessitating detailed expression maps for better understanding.

Purpose of the Study:

• To review methods for quantifying genomic imprinting at tissue and single-cell resolutions.
• To highlight techniques for detecting parent-of-origin-dependent expression in the brain.
• To explore advancements in epigenomic technologies for studying imprinting in individual brain cells.

Main Methods:

• Bulk RNA-sequencing for transcriptome-wide parent-of-origin expression analysis.
• Single-cell RNA-sequencing (scRNA-seq) for cell-resolution imprinting detection.
• Genetic reporters, molecular probes, and single-cell epigenomics (DNA methylation, histone modifications, chromatin conformation).

Main Results:

• Bulk RNA-sequencing is a primary tool for detecting parent-of-origin expression, with established protocols for mouse models.
• scRNA-seq and other single-cell methods enable detailed mapping of imprinting in individual brain cells.
• Emerging sc-multimodal omics approaches integrate multiple epigenetic features for comprehensive imprinting analysis.

Conclusions:

• Accurate mapping of parent-of-origin-dependent gene expression and epigenetic signatures is vital for understanding brain function and disorders.
• A range of methods, from bulk to single-cell resolution, are available for studying genomic imprinting in the brain.
• Advanced epigenomic and multimodal omics technologies promise significant insights into the role of genomic imprinting in individual brain cells.