Single-cell multimodal profiling reveals cellular epigenetic heterogeneity

Nat Methods. 2016 Oct;13(10):833-6. doi: 10.1038/nmeth.3961. Epub 2016 Aug 15.


Sample heterogeneity often masks DNA methylation signatures in subpopulations of cells. Here, we present a method to genotype single cells while simultaneously interrogating gene expression and DNA methylation at multiple loci. We used this targeted multimodal approach, implemented on an automated, high-throughput microfluidic platform, to assess primary lung adenocarcinomas and human fibroblasts undergoing reprogramming by profiling epigenetic variation among cell types identified through genotyping and transcriptional analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cellular Reprogramming / genetics
  • DNA Fingerprinting
  • DNA Methylation / genetics
  • Epigenesis, Genetic / ethics*
  • Fibroblasts
  • Genetic Heterogeneity*
  • Genetic Markers
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Lung Neoplasms / genetics
  • Microchip Analytical Procedures / methods
  • Sequence Analysis, DNA / methods*
  • Single-Cell Analysis / methods*


  • Genetic Markers