期刊
CELL STEM CELL
卷 18, 期 3, 页码 323-329出版社
CELL PRESS
DOI: 10.1016/j.stem.2016.01.019
关键词
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资金
- Jane Coffin Childs Memorial Fund for Medical Research
- UCLA BSCRC Postdoctoral Training Fellowship
- Philip J. Whitcome Fellowship from the UCLA Molecular Biology Institute and a scholarship from the Chinese Scholarship Council
- NIH [R01 HD079546, CIRM RB4-0613, P01 GM099134]
- UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research
Human embryonic stem cells (hESCs) typically exhibit primed'' pluripotency, analogous to stem cells derived from the mouse post-implantation epiblast. This has led to a search for growth conditions that support self-renewal of hESCs akin to hypomethylated naive epiblast cells in human preimplantation embryos. We have discovered that reverting primed hESCs to a hypomethylated naive state or deriving a new hESC line under naive conditions results in the establishment of Stage Specific Embryonic Antigen 4 (SSEA4)-negative hESC lines with a transcriptional program resembling the human pre-implantation epiblast. In contrast, we discovered that the methylome of naive hESCs in vitro is distinct from that of the human epiblast in vivo with loss of DNA methylation at primary imprints and a lost memory'' of the methylation state of the human oocyte. This failure to recover the naive epiblast methylation landscape appears to be a consistent feature of self-renewing hypomethylated naive hESCs in vitro.
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