First Author | Ma S | Year | 2018 |
Journal | Nat Biomed Eng | Volume | 2 |
Issue | 3 | Pages | 183-194 |
PubMed ID | 29963329 | Mgi Jnum | J:356063 |
Mgi Id | MGI:7762155 | Citation | Ma S, et al. (2018) Cell-type-specific brain methylomes profiled via ultralow-input microfluidics. Nat Biomed Eng 2(3):183-194 |
abstractText | Methylomic analyses typically require substantial amounts of DNA, thus hindering studies involving scarce samples. Here, we show that microfluidic diffusion-based reduced representative bisulfite sequencing (MID-RRBS) permits high-quality methylomic profiling with nanogram-to-single-cell quantities of starting DNA. We used the microfluidic device, which allows for efficient bisulfite conversion with high DNA recovery, to analyse genome-wide DNA methylation in cell nuclei isolated from mouse brains and sorted into NeuN+ (primarily neuronal) and NeuN- (primarily glial) fractions, and to establish cell-type-specific methylomes. Genome-wide methylation and methylation in low-CpG-density promoter regions showed distinct patterns for NeuN+ and NeuN- fractions from the mouse cerebellum. The identification of substantial variations in the methylomic landscapes of the NeuN+ fraction of the frontal cortex of mice chronically treated with an atypical antipsychotic drug suggests that this technology can be broadly used for cell-type-specific drug profiling and for the study of drug-methylome interactions. |