Evidence map›Paper›PMID 41565642›Full record

ArticleNature communications2026

Divergent aging of nulliparous and parous mammary glands reveals IL33+ hybrid epithelial cells.

Andrew Olander, Paloma Medina, Veronica Haro Acosta, Sara Kaushik, Matijs Dijkgraaf, Shaheen S Sikandar

Abstract read
In one paragraph

Article in Nature communications, 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

6 authors.

Andrew OlanderDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Paloma MedinaDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Veronica Haro AcostaDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Sara KaushikDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Matijs DijkgraafDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA.
Shaheen S SikandarDepartment of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, CA, USA. ssikanda@ucsc.edu.ORCID 0000-0003-1867-6378

Funding

Molecular mechanisms regulating LMO2+ metastasis initiating cellsR37CA269754 · NCI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Shaheen Sikandar · 2023 to 2026
$1.4M
Determining the effects of pregnancy and aging on the mammary glandF31CA294932 · NCI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Andrew Olander · 2025 to 2026
$86k
NCI NIH HHS F31 CA294932NCI NIH HHS R37 CA269754
6 · The paper itself

Abstract

Aging increases breast cancer risk while an early first pregnancy reduces a woman's life-long risk. Several studies have explored the effect of either aging or pregnancy on mammary stem/progenitor cells, however, the combined effect of both remains unclear. Here, we interrogate the functional and transcriptomic changes at single-cell resolution in the mammary gland of aged nulliparous and parous mice to discover that pregnancy normalizes age-related imbalances in lineage composition, while also inducing a differentiated cell state. Importantly, we uncover a minority population of Il33-expressing epithelial cells that express both luminal and basal markers (i.e. hybrid), which accumulate in aged nulliparous mice but are significantly reduced in aged parous mice. Functionally, IL33 treatment of mammary epithelial cells from young mice phenocopies aged nulliparous epithelial cells, induces proliferation and promotes formation of organoids with Trp53 knockdown. Collectively, our study demonstrates that pregnancy blocks the age-associated imbalances in lineage integrity in the basal layer, including a decrease in Il33+ hybrid cells, that could potentially contribute to pregnancy-induced breast cancer protection.

Indexed as

AgingEpithelial CellsInterleukin-33Mammary Glands, AnimalAnimalsCell DifferentiationCell LineageCell ProliferationFemaleMiceParityPregnancyTumor Suppressor Protein p53Il33 protein, mouseInterleukin-33Trp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID41565642
PMCPMC12923676

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LicenceCC BY
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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.