title: Simultaneous profiling of transcriptome and DNA methylome from a single cell.
abstract: BACKGROUND
  Single-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.
  
  
  RESULTS
  Here, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.
  
  
  CONCLUSIONS
  Our method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA.|Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA.|Division of Oral Biology and Medicine, Laboratory of Molecular Signaling, University of California Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: An
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Du
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Ganlu
authors.initials: G
authors.lastname: Hu
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xue
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China.
authors.forename: Xianmin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Division of Oral Biology and Medicine, Laboratory of Molecular Signaling, University of California Los Angeles, Los Angeles, CA, 90095, USA.
authors.forename: Cun-Yu
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China. xuezg@tongji.edu.cn.|Suzhou Institute, Tongji University, Suzhou, Jiangsu Province, 215101, China. xuezg@tongji.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, UCLA, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA. gfan@mednet.ucla.edu.
authors.forename: Guoping
authors.initials: G
authors.lastname: Fan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018899:CpG Islands; D019175:DNA Methylation; D020869:Gene Expression Profiling / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D059467:Transcriptome
keywords: Dorsal root ganglion; Gene regulation; Sensory neurons; Single-cell methylome; Single-cell transcriptome