Mapping the epigenome of the neural progenitors in the embryonic mouse forebrain using cell sorting and single cell transcriptomics to characterize interneuron diversity

The epigenetic landscape is continually changing during cell proliferation and differentiation throughout development. A common theme emerging from genome-wide association studies (GWAS) is that polymorphisms linked to various diseases are enriched in non-coding regions in the genomes, such as enhancers. Many genes associated with neurological and psychiatric diseases are expressed during embryonic development, and particularly in GABAergic inhibitory interneurons. A comprehensive characterization of epigenomic organization in the embryonic mouse forebrain will enhance our understanding of normal development and provide insight into mechanisms of neurological disease.

In this webinar, Dr Timothy Petros from the NIH, will discuss his research on how intrinsic genetic programs and environmental signals interact to generate interneuron diversity. His group uses the SH800 Cell Sorter to enrich cells and nuclei suspensions from brain dissections. The Petros Lab has performed single-cell chromatin accessibility (snATAC-seq) and transcriptome (scRNA-seq) profiles from four regions of the embryonic mouse forebrain (MGE, LGE, CGE, and cortex) that give rise to distinct neuronal subtypes.

Using this approach, they identified thousands of differentially accessible peaks, many restricted to distinct progenitor cell types and/or brain regions. This dataset defines a ‘ground truth’ epigenomic landscape and reveals a diverse chromatin landscape. The data can be used to explore how perturbation of gene regulation in GABAergic inhibitory interneuron progenitors affects gene expression, chromatin organization, and, ultimately, cell fate.

Key learning objectives

• Understand how to characterize changes in chromatin accessibility at enhancers and promoters that are tightly coupled to transcript abundance during neurodevelopment
• Learn how a single-cell assay for transposase-accessible chromatin with sequencing (scATAC-Seq), in combination with Cut&Tag and Hi-C/Capture-C, can be used to generate an ‘Epigenome Atlas’ of the embryonic mouse brain
• Identify strategies for rapid isolation of single cells or nuclei from embryonic mouse brain with microfluidics-based cell sorting for use in transcriptional profiling of the brain progenitor cells

Who should attend?

This webinar will provide insights for researchers who want to learn about the strategies for the characterization of the epigenetic landscape during embryonic neurogenesis and the methodologies used for successfully generating an epigenome atlas.

Certificate of attendance

All webinar participants can request a certificate of attendance, including a learning outcomes summary, for continuing education purposes.