Evidence map›Paper›PMID 41193641›Full record

ArticleThe EMBO journal2026

Notch signaling is a driver of glandular stem cell activity and regenerative migration after damage.

Davide Cinat, Rufina Maturi, Jeremy P Gunawan, Anne L Jellema-de Bruin, Laura Kracht, Paola Serrano Martinez, Yi Wu, Abel Soto-Gamez, Marc-Jan van Goethem, Inge R Holtman and 3 more

Abstract read
In one paragraph

Article in The EMBO journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

13 authors.

Davide CinatDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands. d.cinat@stanford.edu.ORCID 0000-0001-8005-767X
Rufina MaturiDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.ORCID 0009-0006-0493-3651
Jeremy P GunawanDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Anne L Jellema-de BruinDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Laura KrachtDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Paola Serrano MartinezDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Yi WuDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Abel Soto-GamezDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.ORCID 0000-0001-8975-1377
Marc-Jan van GoethemDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Inge R HoltmanDepartment of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.
Sarah PringleDepartment of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands.ORCID 0000-0002-0779-1680
Lara BarazzuolDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands. l.barazzuol@umcg.nl.ORCID 0000-0002-6538-2383
Rob P CoppesDepartment of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, 9713 GZ, The Netherlands. r.p.coppes@umcg.nl.ORCID 0000-0001-5503-1064

Funding

IBA PPP-2021-27KWF Kankerbestrijding (DCS) 12092
6 · The paper itself

Abstract

Organoid models have significantly enhanced our understanding of adult stem cell function, however, uncovering regulatory mechanisms governing rare and often quiescent stem cells in glandular organs remains challenging. Here, we employ an integrative multi-omics approach, combining single-cell RNA sequencing, bulk ATAC and RNA sequencing, to profile the cellular populations and signaling pathways characterizing a mouse salivary gland organoid model across different temporal stages and after radiation-induced damage. Our findings identify Sox9- and Itgb1/Cd44-expressing cells as primitive adult stem/progenitor populations with a critical migratory role in tissue repair. Notch signaling is a key driver of self-renewal and migration in response to irradiation. Additionally, scRNA-seq analysis of irradiated salivary gland tissue confirms these findings in an in vivo setting. Extending these findings to murine and patient-derived salivary, mammary and thyroid gland organoids, we reveal the conserved role of Notch signaling in coordinating stem/progenitor cell-mediated regeneration across glandular tissues. These insights position Notch signaling as a central regulator of glandular stem cell-like populations and as a promising therapeutic target for enhancing glandular tissue regeneration following cancer therapies.

Indexed as

Cell MovementReceptors, NotchRegenerationSalivary GlandsSignal TransductionStem CellsAnimalsHumansHyaluronan ReceptorsIntegrin beta1MiceOrganoidsSingle-Cell AnalysisSOX9 Transcription FactorCd44 protein, mouseHyaluronan ReceptorsIntegrin beta1Receptors, NotchSox9 protein, mouseSOX9 Transcription FactorAdult Stem CellsCell MigrationGlandular OrganoidsNotch SignalingRadiotherapy

Identifiers

PMID41193641
PMCPMC12811363

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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.