Evidence map›Paper›PMID 30606231›Full record

ArticleEpigenetics & chromatin2019

Specific functions of TET1 and TET2 in regulating mesenchymal cell lineage determination.

Dimitrios Cakouros, Sarah Hemming, Kahlia Gronthos, Renjing Liu, Andrew Zannettino, Songtao Shi, Stan Gronthos

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

51 citing papers in PubMed, 79 citations in OpenAlex.

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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

7 authors at 3 institutions in 2 countries.

Dimitrios CakourosMesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5000, Australia.
Sarah HemmingMesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5000, Australia.
Kahlia GronthosMesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5000, Australia.
Renjing LiuAgnes Ginges Laboratory for Diseases of the Aorta, Centenary Institute for Cancer Medicine and Cell Biology, University of Sydney, Sydney, NSW, 2042, Australia.
Andrew ZannettinoSouth Australian Health and Medical Research Institute, Adelaide, SA, 5000, Australia.
Songtao ShiDepartment of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Stan GronthosMesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, 5000, Australia. stan.gronthos@adelaide.edu.au.ORCID 0000-0002-6225-3084
South Australian Health and Medical Research Institute · AUThe University of Sydney · AUUniversity of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 5 hydroxymethylation (5hmC) mark and TET DNA dioxygenases play a pivotal role in embryonic stem cell differentiation and animal development. However, very little is known about TET enzymes in lineage determination of human bone marrow-derived mesenchymal stem/stromal cells (BMSC). We examined the function of all three TET DNA dioxygenases, responsible for DNA hydroxymethylation, in human BMSC cell osteogenic and adipogenic differentiation.

resultsWe used siRNA knockdown and retroviral mediated enforced expression of TET molecules and discovered TET1 to be a repressor of both osteogenesis and adipogenesis. TET1 was found to recruit the co-repressor proteins, SIN3A and the histone lysine methyltransferase, EZH2 to osteogenic genes. Conversely, TET2 was found to be a promoter of both osteogenesis and adipogenesis. The data showed that TET2 was directly responsible for 5hmC levels on osteogenic and adipogenic lineage-associated genes, whereas TET1 also played a role in this process. Interestingly, TET3 showed no functional effect in BMSC osteo-/adipogenic differentiation. Finally, in a mouse model of ovariectomy-induced osteoporosis, the numbers of clonogenic BMSC were dramatically diminished corresponding to lower trabecular bone volume and reduced levels of TET1, TET2 and 5hmC.

conclusionThe present study has discovered an epigenetic mechanism mediated through changes in DNA hydroxymethylation status regulating the activation of key genes involved in the lineage determination of skeletal stem cells, which may have implications in BMSC function during normal bone regulation. Targeting TET molecules or their downstream targets may offer new therapeutic strategies to help prevent bone loss and repair following trauma or disease.

Indexed as

Cell Differentiation5-MethylcytosineAdipogenesisAnimalsCells, CulturedDioxygenasesDNA-Binding ProteinsDNA MethylationEnhancer of Zeste Homolog 2 ProteinFemaleHumansMesenchymal Stem CellsMiceMice, Inbred C57BLMixed Function OxygenasesOsteogenesis5-hydroxymethylcytosine5-MethylcytosineDioxygenasesDNA-Binding ProteinsEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanMixed Function OxygenasesProto-Oncogene ProteinsRepressor ProteinsSIN3A transcription factorSin3 Histone Deacetylase and Corepressor ComplexTET1 protein, humanTET2 protein, humanEpigeneticsHydroxymethylationMesenchymal stem cellsOsteogenesisOsteoporosisTET

Identifiers

PMID30606231
PMCPMC6317244
OpenAlexW2914844813

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.