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Record W4415928668 · doi:10.1038/s44318-025-00607-w

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

2025· article· en· W4415928668 on OpenAlexaff
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, Sarah Pringle, Lara Barazzuol, Robert P. Coppes

Bibliographic record

VenueThe EMBO Journal · 2025
Typearticle
Languageen
FieldMedicine
TopicSalivary Gland Disorders and Functions
Canadian institutionsOttawa Hospital
FundersUniversitair Medisch Centrum GroningenKWF Kankerbestrijding
KeywordsNotch signaling pathwayStem cellOrganoidRegeneration (biology)RegulatorSignal transductionAdult stem cellHes3 signaling axis

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.244
Threshold uncertainty score0.159

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.245
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes1
Has abstractyes

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