Evidence map›Paper›PMID 41526722›Full record

ArticleCell death and differentiation2026

The PIDDosome controls cardiomyocyte polyploidization during postnatal heart development.

M Leone, N Kinz, F Eichin, D Obwegs, V C Sladky, V Z Braun, R Hirschberger, D Rizzotto, L Englmaier, C Manzl and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

25 authors.

M LeoneBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria. macileo@hotmail.com.ORCID http://orcid.org/0000-0001-6839-6265
N KinzBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.
F EichinBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0000-0002-0085-1097
D ObwegsBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0009-0009-0011-073X
V C SladkyBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.
V Z BraunBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.ORCID http://orcid.org/0009-0006-0858-3775
R HirschbergerBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria.
D RizzottoCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID http://orcid.org/0000-0003-0106-7496
L EnglmaierCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
C ManzlInstitute of Neuropathology and Neuromolecularpathology, Medical University of Innsbruck, Innsbruck, Austria.
K MoosInstitute of Medical Bioinformatics and Systems Medicine (IBSM), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
J MergnerTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-4332-1280
P GiansantiTranslaTUM, Center for Translational Cancer Research, Technical University of Munich, Munich, Germany.
N Martinez-GarciaInstituto de Biomedicina and Departamento de Producción Animal, Universidad de León, León, Spain.ORCID http://orcid.org/0000-0001-9653-9745
M M MarquesInstituto de Biomedicina and Departamento de Producción Animal, Universidad de León, León, Spain.ORCID http://orcid.org/0000-0003-2818-035X
E D JacototInserm U1268, Medicinal Chemistry and Translational Research, Paris, France.ORCID http://orcid.org/0000-0002-5301-1569
L EblahedSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.
R YousifSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.
M K WrightSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.
D DawoodSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.
L S MaupomeSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.
C SavkoSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.
M BoerriesInstitute of Medical Bioinformatics and Systems Medicine (IBSM), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-3670-0602
M A SussmanSan Diego State University Heart Institute and Department of Biology, San Diego State University, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-0104-4799
A VillungerBiocenter, Institute for Developmental Immunology, Medical University of Innsbruck, Innsbruck, Austria. andreas.villunger@i-med.ac.at.ORCID http://orcid.org/0000-0001-8259-4153

Funding

Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) I6662Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) M3115BAustrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P36658Deutsche Forschungsgemeinschaft (German Research Foundation) CRC/TRR353Deutsche Forschungsgemeinschaft (German Research Foundation) INST 95/1650-1
6 · The paper itself

Abstract

The adult mammalian heart is characterized by post-mitotic polyploid cardiomyocytes (CMs). Understanding how CMs regulate cell cycle exit and polyploidy can help developing new heart regenerative therapies. Here, we uncover that the PIDDosome, a multi-protein complex activating the endopeptidase Caspase-2, helps to implement a CM-specific differentiation program that limits ploidy during postnatal heart development. DNA content analyses show that cell-autonomous PIDDosome loss causes an increase in nuclear and cellular CM ploidy. Increased ploidy does not affect cardiac structure nor function in early adulthood, but correlates with a modest reduction in cardiac performance in aged mice. PIDDosome-imposed polyploidy control commences at postnatal day 7 (P7), reaching a plateau by P14. PIDDosome activation requires ANKRD26, targeting PIDD1 to mother centrioles. Opposite to prior observations in liver development, the PIDDosome limits CM polyploidization in a p53-independent manner but reliant on induction of p21/Cdkn1a, a notion supported by nuclear RNA sequencing and genetic deletion experiments. Our results provide new insights how proliferation of polyploid CMs is restricted during postnatal heart development.

Indexed as

Death Domain Receptor Signaling Adaptor ProteinsHeartMyocytes, CardiacPolyploidyAnimalsCaspase 2Cell DifferentiationCyclin-Dependent Kinase Inhibitor p21MiceTumor Suppressor Protein p53Caspase 2Cyclin-Dependent Kinase Inhibitor p21Death Domain Receptor Signaling Adaptor ProteinsPidd1 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID41526722
PMCPMC13246752

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.