BMC Genomics | |
Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming | |
Hehuang Xie2  Xuemei Lu1  Ming-An Sun3  Cuiyun Zhang1  Xiaojian Shao1  | |
[1] Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24060, USA;Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, VA 24060, USA | |
关键词: Cellular heterogeneity; Reprogramming; Stem cell; DNA methylation; | |
Others : 1092477 DOI : 10.1186/1471-2164-15-978 |
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received in 2014-06-30, accepted in 2014-10-30, 发布年份 2014 | |
【 摘 要 】
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.
【 授权许可】
2014 Shao et al.; licensee BioMed Central Ltd.
【 预 览 】
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20150128184744927.pdf | 2285KB | download | |
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