Untangling cell-type-specific gene regulation and interpreting disease risk associations using single cell genomics

 

Abstract: 

Transcriptional regulation plays a fundamental role in development and disease. Non-coding regions called cis-regulatory elements (CRE) in the genome such as enhancers and promoters control cell-type-specific gene expression patterns. A large fraction of genetic variants associated with common traits and diseases are enriched in CREs in the human genome. Tissue heterogeneity poses a significant challenge to elucidate cell-type-specific gene regulatory programs. Thus, we have optimized single cell chromatin accessibility workflows to overcome this limitation and generated CREs atlases for a wide variety of tissues including mouse brains and human hearts at single cell resolution. These comprehensive maps revealed regulatory programs and key transcription factors in hundreds of cell types and enabled interpretation and functional validation of noncoding variants associated with complex human traits and diseases.