High-throughput chromatin accessibility profiling at single-cell resolution.
Anja MezgerSandy KlemmIshminder MannKara BrowerAlain MirMagnolia BostickAndrew FarmerPolly FordyceSten LinnarssonWilliam J GreenleafPublished in: Nature communications (2018)
Here we develop a high-throughput single-cell ATAC-seq (assay for transposition of accessible chromatin) method to measure physical access to DNA in whole cells. Our approach integrates fluorescence imaging and addressable reagent deposition across a massively parallel (5184) nano-well array, yielding a nearly 20-fold improvement in throughput (up to ~1800 cells/chip, 4-5 h on-chip processing time) and library preparation cost (~81¢ per cell) compared to prior microfluidic implementations. We apply this method to measure regulatory variation in peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of single cells by hematopoietic cell type.
Keyphrases
- high throughput
- single cell
- rna seq
- induced apoptosis
- cell cycle arrest
- fluorescence imaging
- transcription factor
- gene expression
- endoplasmic reticulum stress
- dna damage
- cell death
- mental health
- genome wide
- physical activity
- high resolution
- oxidative stress
- stem cells
- photodynamic therapy
- bone marrow
- mesenchymal stem cells
- cell therapy
- simultaneous determination