Evidence map›Paper›PMID 42866953›Full record

ArticleNucleic acids research2026

CircACVR2A(2-4) regulates stem cell pluripotency by uncoupling CDK-activating kinase functions.

Stuart Webb, Vanessa M Conn, Eljo Yvette van Battum, Kirsty Kirk, Ashleigh B Geiger, Suman Singh, Marta Gabryelska, Michael J Roach, Shashikanth Marri, He Lin and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

25 authors.

Stuart WebbFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Vanessa M ConnFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Eljo Yvette van BattumDepartment of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.ORCID 0000-0002-3358-5039
Kirsty KirkFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Ashleigh B GeigerAdelaide Centre for Epigenetics, School of Biomedicine, Faculty of Health and Medical Sciences, Adelaide University, Adelaide 5000, Australia.ORCID 0000-0002-0203-1682
Suman SinghFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Marta GabryelskaFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Michael J RoachFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Shashikanth MarriFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
He LinFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Ryan LiuFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Jordyn BinelliFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
John ToubiaCentre for Cancer Biology, an alliance between SA Pathology and the University of South Australia, Adelaide, SA 5000, Australia.ORCID 0000-0002-5135-6504
Jenne TranFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Alex D ColellaFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Thomas ColungaCenter for Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, United States.
Michael KulikCenter for Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, United States.
Cedric BardyFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.
Lachlan JollySchool of Pharmacy and Biomedicine, Adelaide University, Adelaide, SA 5000, Australia.
R Jeroen PasterkampDepartment of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Ross A McKinnonFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.ORCID 0000-0002-3725-793X
Stephen DaltonSchool of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong,China.
Lasse S KristensenDepartment of Biomedicine, Aarhus University, Aarhus 8000, Denmark.
Adrienne E SullivanAdelaide Centre for Epigenetics, School of Biomedicine, Faculty of Health and Medical Sciences, Adelaide University, Adelaide 5000, Australia.
Simon J ConnFlinders Health and Medical Research Institute, College of Medicine & Public Health, Flinders University, Bedford Park, SA 5042, Australia.ORCID 0000-0002-1376-4515

Funding

Australian Research Council Future Fellowship FT160100318Lundbeck Foundation R307-2018-3433National Health and Medical Research Council GNT1144250Netherlands Organization for Scientific Research ALW-VICI 865.14.004NHMRC Investigator Leadership GNT1198014NHMRC Investigator Leadership GNT2042423Roadmap from Neurogenetics to Neurobiology NWO: 024.004.012South Australian immunoGENomics Cancer Institute
6 · The paper itself

Abstract

Differentiation of stem cells is driven by tightly coordinated transcriptional programs, yet the contribution of circular RNAs (circRNAs) to lineage specification remains poorly defined. Here, we profiled circRNA and messenger RNA expression during differentiation of human embryonic stem cells into five germ layer-derived lineages. Targeted silencing of dynamically regulated circRNAs revealed that depletion of circACVR2A(2-4), but not its linear counterpart, induced rapid loss of pluripotency accompanied by neuroectoderm-biased differentiation, phenotypically and transcriptionally. Mechanistically, circACVR2A(2-4) interacts with cyclin H within the cyclin-dependent kinase (CDK)-activating kinase (CAK) complex to modulate RNA polymerase II (RNAPII) phosphorylation independently of CDK activation, with lineage commitment consistent with destabilization of RNAPII pausing at poised neuroectodermal loci. In vivo, circACVR2A(2-4) silencing impaired neuronal migration in the embryonic mouse brain and attenuated glioblastoma progression in mouse orthotopic xenografts. Together, these findings identify a circRNA-mediated mechanism that uncouples CAK complex activity to modulate stem cell fate.

Indexed as

Human Embryonic Stem CellsPluripotent Stem CellsRNAAnimalsCell DifferentiationCell LineageCyclin-Dependent Kinase-Activating KinaseGlioblastomaHumansMicePhosphorylationRNA, CircularRNA Polymerase IICyclin-Dependent Kinase-Activating KinaseRNARNA, CircularRNA Polymerase II

Identifiers

PMID42866953
PMCPMC13659242

What OpenQuestion holds

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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.