Lih Feng Cheow1, Elise T Courtois2,10, Yuliana Tan2,10, Ramya Viswanathan1,10, Qiaorui Xing1,3,10, Rui Zhen Tan4, Daniel S W Tan2,5, Paul Robson2,6,7,
Yuin-Han Loh1,6, Stephen R Quake8,9 &
William F Burkholder1
1 Institute of Molecular and Cell Biology, Singapore.
2 Genome Institute of Singapore, Singapore.
3 School of Biological Sciences, Nanyang Technological University, Singapore.
4 Bioinformatics Institute, Singapore.
5 National Cancer Centre Singapore, Singapore.
6 Department of Biological Sciences, National University of Singapore, Singapore.
7 The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
8 Departments of Bioengineering and Applied Physics, Stanford University, Stanford, California, USA.
8 Howard Hughes Medical Institute, Stanford, California, USA.
10 These authors contributed equally to this work.
Correspondence should be addressed to L.F.C. (email@example.com),
S.R.Q. (firstname.lastname@example.org) or W.F.B. (email@example.com).
Published online in Nature Methods on 15 August 2016.
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.
Figure. 1. sc-GEM analysis of human cellular reprogramming.
(a) Cell collection schedule during the reprogramming process.
Cells sorted for the TRA-1-60 pluripotency marker and additional
reference cell lines are shown. (b) Dynamics of single-cell gene
expression (top) and DNA methylation (bottom) during reprogramming. Single cells (columns) are grouped according to time of collection. Loci are arranged into pluripotent, intermediate and somatic groups
based on gene expression pattern (top) and are grouped according to whether they undergo de novo methylation or demethylation during reprogramming (bottom). Gray boxes represent methylated loci, and white boxes represent unmethylated loci.
For more information on William F. BURKHOLDER / Stephen QUAKE 's lab, please click here.