Evidence map›Paper›PMID 34995500›Full record

ArticleStem cell reports2022

DOT1L inhibition enhances pluripotency beyond acquisition of epithelial identity and without immediate suppression of the somatic transcriptome.

Coral K Wille, Rupa Sridharan

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 22 citations in OpenAlex.

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  17. Connecting the DOTs on Cell Identity.Frontiers in cell and developmental biology · 2022
    Review
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

2 authors at 2 institutions in 1 country.

Coral K WilleWisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA.
Rupa SridharanWisconsin Institute for Discovery, University of Wisconsin, 330 North Orchard Street, Room 2118, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI 53705, USA. Electronic address: rsridharan2@wisc.edu.
University of Wisconsin–Madison · USWisconsin Institutes for Discovery · US

Funding

R01 Renewal: Collaboration of chromatin remodeling and signaling pathways in pluripotencyR01GM113033 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SRIDHARAN, RUPA · 2015 to 2023
$2.9M
NIGMS NIH HHS R01 GM113033
6 · The paper itself

Abstract

Inhibiting the histone 3 lysine 79 (H3K79) methyltransferase, disruptor of telomeric silencing 1-like (DOT1L), increases the efficiency of reprogramming somatic cells to induced pluripotent stem cells (iPSCs). Here, we find that, despite the enrichment of H3K79 methylation on thousands of actively transcribed genes in somatic cells, DOT1L inhibition (DOT1Li) does not immediately cause the shutdown of the somatic transcriptional profile to enable transition to pluripotency. Contrary to the prevalent view, DOT1Li promotes iPSC generation beyond the mesenchymal to epithelial transition and even from already epithelial cell types. DOT1Li is most potent at the midpoint of reprogramming in part by repressing Nfix that persists at late stages of reprogramming. Importantly, regulation of single genes cannot substitute for DOT1Li, demonstrating that H3K79 methylation has pleiotropic effects in maintaining cell identity.

Indexed as

TranscriptomeAnimalsCellular ReprogrammingDown-RegulationEmbryo, MammalianEmbryonic Stem CellsFemaleFibroblastsHistone-Lysine N-MethyltransferaseHistonesInduced Pluripotent Stem CellsMaleMethylationMiceRNA InterferenceRNA, Small InterferingDot1l protein, mouseHistone-Lysine N-MethyltransferaseHistonesRNA, Small InterferingDOT1LH3K79 methylationiPSCs induced pluripotent stem cellsNFIXreprogramming

Identifiers

PMID34995500
PMCPMC8828533
OpenAlexW4206813594

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.