Evidence map›Paper›PMID 30017590›Full record

ArticleCell stem cell2018

Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming.

Benjamin A Schwarz, Murat Cetinbas, Kendell Clement, Ryan M Walsh, Sihem Cheloufi, Hongcang Gu, Jan Langkabel, Akihide Kamiya, Hubert Schorle, Alexander Meissner and 2 more

Abstract read
In one paragraph

Article in Cell stem cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
–field-weighted citation impact
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

49 citing papers in PubMed.

  1. Article
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  10. Vitamin BNature metabolism · 2023
    Article
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  15. Article
  16. Post-transcriptional regulation in cranial neural crest cells expands developmental potential.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Article
  18. Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023
    Review
  19. Article
  20. Article
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

12 authors.

Benjamin A SchwarzDepartment 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; Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Murat CetinbasDepartment of Molecular Biology, Cancer Center, and Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Kendell ClementDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ryan M WalshDepartment 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.
Sihem CheloufiDepartment 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.
Hongcang GuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jan LangkabelUniversity of Bonn Medical School, Institute of Pathology, Department of Developmental Pathology, Bonn, Germany.
Akihide KamiyaDepartment of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, Japan.
Hubert SchorleUniversity of Bonn Medical School, Institute of Pathology, Department of Developmental Pathology, Bonn, Germany.
Alexander MeissnerHarvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ruslan I SadreyevDepartment of Molecular Biology, Cancer Center, and Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Konrad HochedlingerDepartment 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: hochedlinger@molbio.mgh.harvard.edu.

Funding

ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI CHRISTOPHER P DUGGAN · 1994 to 2026
$31.6M
Regulatory Roles and Dynamics of Nuclear long-noncoding RNAs in PluripotencyP01GM099117 · NIGMS · HARVARD UNIVERSITY · PI MEISSNER, ALEXANDER · 2011 to 2021
$21.2M
Roles of sumoylation and alternative polyadenylation in cellular reprogrammingP01GM099134 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PLATH, KATHRIN · 2011 to 2021
$20.3M
Center for Cell CircuitsP50HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI REGEV, AVIV · 2011 to 2015
$15.6M
Transcription Factor Induced ReprogrammingR01HD058013 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI HOCHEDLINGER, KONRAD · 2010 to 2019
$4.4M
National Human Genome Research Institute P50 HG006193National Institute of General Medical Sciences P01 GM099117NICHD NIH HHS R01 HD058013NIDDK NIH HHS P30 DK040561NIGMS NIH HHS P01 GM099134
6 · The paper itself

Abstract

Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is typically very inefficient, complicating mechanistic studies. We identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors (e.g., Tfap2c and Bex2) that are important for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed an early wave of DNA demethylation that is uncoupled from de novo methylation of somatic regions late in reprogramming. Our study underscores the importance of investigating rare intermediates poised to produce iPSCs, provides insights into reprogramming mechanisms, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change.

Indexed as

Cellular ReprogrammingAnimalsCells, CulturedFemaleInduced Pluripotent Stem CellsMaleMiceMice, Inbred BALB Ccell surface antigenscellular reprogrammingchromatinDNA methylationepigenomicsgene expressioninduced pluripotent stem cellstranscription factors

Identifiers

PMID30017590
PMCPMC6086589

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Registered trials

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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.