Evidence map›Paper›PMID 42527402›Full record

ArticleCell death discovery2026

Physiological re-replication during human stem cell differentiation.

Marie Minet, Amila Beganovic, Shusruto Rishik, Elisa Michaeli, Daniela Yildiz, Georges P Schmartz, Paula E Schwarz, Melina Schäfer, Tanja Tänzer, Magali Cucchiarini and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death discovery, 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

14 authors.

Marie Minet *Institute of Human Genetics, Saarland University, Homburg, Germany.ORCID http://orcid.org/0000-0001-6372-5234
Amila Beganovic *Institute of Human Genetics, Saarland University, Homburg, Germany.ORCID http://orcid.org/0009-0005-2371-7033
Shusruto RishikChair of Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
Elisa MichaeliInstitute of Human Genetics, Saarland University, Homburg, Germany.ORCID http://orcid.org/0009-0005-2347-2187
Daniela YildizChair of Molecular Pharmacology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany.
Georges P SchmartzChair of Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
Paula E SchwarzInstitute of Human Genetics, Saarland University, Homburg, Germany.
Melina SchäferInstitute of Human Genetics, Saarland University, Homburg, Germany.
Tanja TänzerChair of Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.
Magali CucchiariniCenter of Experimental Orthopedics, Saarland University Medical Center, Homburg, Germany.
Nicole LudwigChair of Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.ORCID http://orcid.org/0000-0003-4703-7567
Andreas KellerChair of Clinical Bioinformatics, Saarland University, Saarbrücken, Germany.ORCID http://orcid.org/0000-0002-5361-0895
Eckart MeeseInstitute of Human Genetics, Saarland University, Homburg, Germany.
Ulrike FischerInstitute of Human Genetics, Saarland University, Homburg, Germany. ulrike.fischer@uks.eu.ORCID http://orcid.org/0000-0002-7808-9565

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) 469073465Deutsche Forschungsgemeinschaft (German Research Foundation) DFG INST 256/508-1Deutsche Forschungsgemeinschaft (German Research Foundation) DFG INST 256/541-1 FUGGDeutsche Forschungsgemeinschaft (German Research Foundation) DFG INST 256/550-1 FUGBUniversität des Saarlandes (Saarland University) funding open access charge
6 · The paper itself

Abstract

During restricted timeframes in Drosophila development, re-replication occurs as physiological process causing the known developmental gene amplification in Drosophila. Gene amplification has also been found during differentiation in human stem cells but re-replication in human cells has been preferentially associated with tumor related genome instability. Here, we show that re-replication also occurs as physiological process in human stem cells. We used Rerep-Seq and fiber-combing to demonstrate re-replication during the differentiation of human myoblasts into myotubes and during the differentiation of mesenchymal stem cells into adipocytes, osteoblasts, chondrocytes, and neurons. Re-replication was detectable during specific timeframes in all differentiations analyzed. FACS sorting of re-replicating cells showed increased gene expression in re-replicated genome regions. Additionally, re-replicated DNA was identified as extranuclear DNA. This leads us to the hypothesis that cells that do not re-replicate and thus do not face an increased risk of chromosomal instability may ensure higher expression of certain genes and their encoded proteins during differentiation by incorporating re-replicated DNA from neighbouring cells with re-replication. We propose that human stem cells use an ancient re-replication mechanism to efficiently increase gene copy numbers, thereby meeting the heightened protein demands during differentiation.

Identifiers

PMID42527402
PMCPMC13421607

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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.