期刊
CELL STEM CELL
卷 20, 期 5, 页码 706-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2017.03.002
关键词
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资金
- American Cancer Society
- New England Division
- Ellison Foundation Postdoctoral Fellowship [PF-15-130-01-DDC]
- NIH [1F32HD078029-01A1, P01GM099117, R01 HD058013]
- New York Stem Cell Foundation
- Center for Excellence in Genome Science from the NHGRI [1P50HG006193-01]
- HHMI
- Gerald R. and Darlene Jordan Endowed Chair for Regenerative Medicine
Blastocyst-derived embryonic stem cells (ESCs) and gonad-derived embryonic germ cells (EGCs) represent two classic types of pluripotent cell lines, yet their molecular equivalence remains incompletely understood. Here, we compare genome-wide methylation patterns between isogenic ESC and EGC lines to define epigenetic similarities and differences. Surprisingly, we find that sex rather than cell type drives methylation patterns in ESCs and EGCs. Cell fusion experiments further reveal that the ratio of X chromosomes to autosomes dictates methylation levels, with female hybrids being hypomethylated and male hybrids being hypermethylated. We show that the X-linked MAPK phosphatase DUSP9 is upregulated in female compared to male ESCs, and its heterozygous loss in female ESCs leads to male-like methylation levels. However, male and female blastocysts are similarly hypomethylated, indicating that sex-specific methylation differences arise in culture. Collectively, our data demonstrate the epigenetic similarity of sex-matched ESCs and EGCs and identify DUSP9 as a regulator of female-specific hypomethylation.
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