title: Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming.
abstract: BACKGROUND
  Human induced pluripotent stem cells (iPSCs) have a wide range of applications throughout the fields of basic research, disease modeling and drug screening. Epigenetic instable iPSCs with aberrant DNA methylation may divide and differentiate into cancer cells. Unfortunately, little effort has been taken to compare the epigenetic variation in iPSCs with that in differentiated cells. Here, we developed an analytical procedure to decipher the DNA methylation heterogeneity of mixed cells and further exploited it to quantitatively assess the DNA methylation variation in the methylomes of adipose-derived stem cells (ADS), mature adipocytes differentiated from ADS cells (ADS-adipose) and iPSCs reprogrammed from ADS cells (ADS-iPSCs).
  
  
  RESULTS
  We observed that the degree of DNA methylation variation varies across distinct genomic regions with promoter and 5'UTR regions exhibiting low methylation variation and Satellite showing high methylation variation. Compared with differentiated cells, ADS-iPSCs possess globally decreased methylation variation, in particular in repetitive elements. Interestingly, DNA methylation variation decreases in promoter regions during differentiation but increases during reprogramming. Methylation variation in promoter regions is negatively correlated with gene expression. In addition, genes showing a bipolar methylation pattern, with both completely methylated and completely unmethylated reads, are related to the carbohydrate metabolic process, cellular development, cellular growth, proliferation, etc.
  
  
  CONCLUSIONS
  This study delivers a way to detect cell-subset specific methylation genes in a mixed cell population and provides a better understanding of methylation dynamics during stem cell differentiation and reprogramming.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Shao
authors.forename: Cuiyun
authors.initials: C
authors.lastname: Zhang
authors.forename: Ming-An
authors.initials: MA
authors.lastname: Sun
authors.affiliation: Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. luxm@big.ac.cn.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Lu
authors.forename: Hehuang
authors.initials: H
authors.lastname: Xie
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics*; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D018740:Genetic Heterogeneity; D023281:Genomics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D024363:Transcription Initiation Site