Evidence map›Paper›PMID 26853856›Full record

ArticleCell stem cell2016

Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline Memory.

William A Pastor, Di Chen, Wanlu Liu, Rachel Kim, Anna Sahakyan, Anastasia Lukianchikov, Kathrin Plath, Steven E Jacobsen, Amander T Clark

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 1 pooled it
20.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

192 citing papers in PubMed, 1 synthesis or guideline pooled it, 294 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. The making of cells and organs in xenogeneic animal bioreactor.Signal transduction and targeted therapy · 2026
    Review
  4. Article
  5. Article
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  7. Article
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  10. Review
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  16. Review
  17. Review
  18. Article
  19. Article
  20. Why are imprints unstable in pluripotent stem cells?Biochemical Society transactions · 2025
    Article

132 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

William A Pastor *Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles CA 90095.
Di Chen *Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles CA 90095.
Wanlu Liu *Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles CA 90095.
Rachel KimEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California Los Angeles, Los Angeles CA 90095.
Anna SahakyanDepartment of Biological Chemistry, University of California Los Angeles, Los Angeles CA 90095.
Anastasia LukianchikovDepartment of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles CA 90095.
Kathrin PlathEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California Los Angeles, Los Angeles CA 90095.
Steven E JacobsenDepartment of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles CA 90095.
Amander T ClarkDepartment of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles CA 90095.
University of California, Los Angeles · USHoward Hughes Medical Institute · US

Funding

Roles of sumoylation and alternative polyadenylation in cellular reprogrammingP01GM099134 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOCHEDLINGER, KONRAD · 2011 to 2021
$20.3M
Differentiating embryonic stem cells into developing germ lineR01HD079546 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CLARK, AMANDER · 2015 to 2024
$3.7M
Mechanisms of XIST RNA-induced gene silencing in humansF31GM115122 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SAHAKYAN, ANNA · 2015 to 2016
$70k
Howard Hughes Medical InstituteNICHD NIH HHS R01 HD079546NIGMS NIH HHS F31 GM115122NIGMS NIH HHS P01 GM099134
6 · The paper itself

Abstract

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 pre-implantation 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.

Indexed as

DNA MethylationAnimalsBlastocystCell LineHuman Embryonic Stem CellsHumansMiceOocytesPluripotent Stem CellsStage-Specific Embryonic Antigensstage-specific embryonic antigen-4Stage-Specific Embryonic Antigens

Identifiers

PMID26853856
PMCPMC4779431
OpenAlexW2253271165

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.