Evidence map›Paper›PMID 35511867›Full record

ArticleStem cells (Dayton, Ohio)2022

Histone Variant macroH2A1.1 Enhances Nonhomologous End Joining-dependent DNA Double-strand-break Repair and Reprogramming Efficiency of Human iPSCs.

Sebastiano Giallongo, Daniela Řeháková, Tommaso Biagini, Oriana Lo Re, Priyanka Raina, Gabriela Lochmanová, Zbyněk Zdráhal, Igor Resnick, Pille Pata, Illar Pata and 5 more

Open access · greenAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

16 citing papers in PubMed, 33 citations in OpenAlex.

  1. Splice isoforms of the histone variant macroH2A1 differentially regulate hippocampal gene expression and memory formation.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  2. Dynamic Assemblies in Genome Maintenance.Advances in experimental medicine and biology · 2026
    Review
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  12. Liquid Liver Biopsy for Disease Diagnosis and Prognosis.Journal of clinical and translational hepatology · 2023
    Review
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  15. Review
  16. The Role of Epigenetics in Neuroinflammatory-Driven Diseases.International journal of molecular sciences · 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

15 authors at 12 institutions in 5 countries.

Sebastiano GiallongoInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Daniela ŘehákováInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Tommaso BiaginiLaboratory of Bioinformatics, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Oriana Lo ReInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Priyanka RainaIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Gabriela LochmanováCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Zbyněk ZdráhalCentral European Institute of Technology, Masaryk University, Brno, Czech Republic.
Igor ResnickDepartment of Translational Stem Cell Biology, Research Institute of the Medical University of Varna (RIMUV), Varna, Bulgaria.
Pille PataDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
Illar PataDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
Martin MistríkLaboratory of Genome Integrity, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
João Pedro de MagalhãesIntegrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.
Tommaso MazzaDepartment of Translational Stem Cell Biology, Research Institute of the Medical University of Varna (RIMUV), Varna, Bulgaria.
Irena KoutnáInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Manlio VinciguerraInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
Medical University of Varna · BGSt. Anne's University Hospital Brno · CZTallinn University of Technology · EECasa Sollievo della Sofferenza · ITCentral European Institute of Technology · CZCentral European Institute of Technology – Masaryk University · CZGenomics (United Kingdom) · GBInstitute of Molecular and Translational Medicine · CZMasaryk University · CZUniversity Hospital Brno · CZUniversity Hospital St. Marina · BGUniversity of Liverpool · GB

Funding

Wellcome Trust 208375/Z/17/Z
6 · The paper itself

Abstract

DNA damage repair (DDR) is a safeguard for genome integrity maintenance. Increasing DDR efficiency could increase the yield of induced pluripotent stem cells (iPSC) upon reprogramming from somatic cells. The epigenetic mechanisms governing DDR during iPSC reprogramming are not completely understood. Our goal was to evaluate the splicing isoforms of histone variant macroH2A1, macroH2A1.1, and macroH2A1.2, as potential regulators of DDR during iPSC reprogramming. GFP-Trap one-step isolation of mtagGFP-macroH2A1.1 or mtagGFP-macroH2A1.2 fusion proteins from overexpressing human cell lines, followed by liquid chromatography-tandem mass spectrometry analysis, uncovered macroH2A1.1 exclusive interaction with Poly-ADP Ribose Polymerase 1 (PARP1) and X-ray cross-complementing protein 1 (XRCC1). MacroH2A1.1 overexpression in U2OS-GFP reporter cells enhanced specifically nonhomologous end joining (NHEJ) repair pathway, while macroH2A1.1 knock-out (KO) mice showed an impaired DDR capacity. The exclusive interaction of macroH2A1.1, but not macroH2A1.2, with PARP1/XRCC1, was confirmed in human umbilical vein endothelial cells (HUVEC) undergoing reprogramming into iPSC through episomal vectors. In HUVEC, macroH2A1.1 overexpression activated transcriptional programs that enhanced DDR and reprogramming. Consistently, macroH2A1.1 but not macroH2A1.2 overexpression improved iPSC reprogramming. We propose the macroH2A1 splicing isoform macroH2A1.1 as a promising epigenetic target to improve iPSC genome stability and therapeutic potential.

Indexed as

HistonesInduced Pluripotent Stem CellsAnimalsDNADNA RepairEndothelial CellsHumansMiceX-ray Repair Cross Complementing Protein 1DNAHistonesMACROH2A1 protein, humanX-ray Repair Cross Complementing Protein 1XRCC1 protein, humancell reprogrammingDNA damageinduced pluripotent stem cellsmacroH2A1.1

Identifiers

PMID35511867
PMCPMC9199840
OpenAlexW4205983171

What OpenQuestion holds

Textmetadata
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.