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Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline Memory
Open accessAbstract
Summary 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 naïve epiblast cells in human pre-implantation embryos. We have discovered that reverting primed hESCs to a hypomethylated naïve state or deriving a new hESC line under naïve 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 naïve hESCs in vitro is distinct from 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 naïve epiblast methylation landscape appears to be a consistent feature of self-renewing hypomethylated naïve hESCs in vitro.
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Self-citation
Metadata
- Authors
- Pastor, W. A., Chen, D., Liu, W., Kim, R., Sahakyan, A., Lukianchikov, A., Plath, K., Jacobsen, S. E., & Clark, A. T.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 18
- Issue
- 3
- Pages
- 323-329
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2253271165
- Cited by
- 283
- References
- 25
- FWCI
- 16.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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