Journal
CELL
Volume 161, Issue 6, Pages 1425-1436Publisher
CELL PRESS
DOI: 10.1016/j.cell.2015.05.012
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Funding
- NIH [NIH/NICHD HD058047, NIH/NICHD HD079546]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
- Academia Sinica
- National Health Research Institutes, Taiwan [NHR-IEXI03-10324SC]
- California Institute for Regenerative Medicine (CIRM) [TG2-01169]
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Global DNA demethylation in humans is a fundamental process that occurs in pre-implantation embryos and reversion to naive ground state pluripotent stem cells (PSCs). However, the extent of DNA methylation reprogramming in human germline cells is unknown. Here, we performed whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq) of human prenatal germline cells from 53 to 137 days of development. We discovered that the transcriptome and methylome of human germline is distinct from both human PSCs and the inner cell mass (ICM) of human blastocysts. Using this resource to monitor the outcome of global DNA demethylation with reversion of primed PSCs to the naive ground state, we uncovered hotspots of ultra-low methylation at transposons that are protected from demethylation in the germline and ICM. Taken together, the human germline serves as a valuable in vivo tool for monitoring the epigenome of cells that have emerged from a global DNA demethylation event.
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