| Autor: |
Wei Feng Ma, Euan A. Ashley, Johan L.M. Björkegren, Emily Farber, Soumya Kundu, Clint L. Miller, Sheng'en Hu, Thomas Quertermous, Anshul Kundaje, Lijiang Ma, Jason C. Kovacic, Aloke V. Finn, Chani J. Hodonsky, Adam W. Turner, Suna Onengut-Gumuscu, Nicholas J. Leeper, Jose Verdezoto Mosquera, Chongzhi Zang, Gaelle Auguste, Nicolas G. Lopez, Saikat Ghosh, Doris Wong, Katia Sol-Church |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.06.07.447388 |
| Popis: |
Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across several cell types. Genome-wide association studies (GWAS) have identified over 170 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements (CREs). Here, we applied single-cell ATAC-seq to profile 28,316 cells across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell type-specific elements, transcription factors, and prioritized functional CAD risk variants via quantitative trait locus and sequence-based predictive modeling. We identified a number of candidate mechanisms for smooth muscle cell transition states and identified putative binding sites for risk variants. We further employed CRE to gene linkage to nominate disease-associated key driver transcription factors such as PRDM16 and TBX2. This single cell atlas provides a critical step towards interpreting cis-regulatory mechanisms in the vessel wall across the continuum of CAD risk. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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