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DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells. | LitMetric

DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells.

Cell Stem Cell

Department of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address:

Published: May 2017

AI Article Synopsis

  • The study investigates the differences and similarities in epigenetic patterns between embryonic stem cells (ESCs) and embryonic germ cells (EGCs), focusing on genome-wide methylation.
  • It finds that sex, rather than cell type, largely influences methylation patterns, with female cells showing lower levels of methylation compared to male cells.
  • The research identifies the X-linked gene DUSP9 as a key factor that regulates this female-specific hypomethylation and concludes that sex-specific methylation differences develop during cell culture.

Article Abstract

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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524993PMC
http://dx.doi.org/10.1016/j.stem.2017.03.002DOI Listing

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