ArticleNature communications2024
Physiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Molecular regulation of plant endoreduplication: core mechanisms and their upstream control.Plant molecular biology · 2026Review
- Epithelial cell fusion is required for tissue repair following UV-A irradiation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Growth under pressure: The pros and cons of polyploidy induced by stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Review
- Article
- Defining breast epithelial cell types in the single-cell era.Developmental cell · 2025Review
- Morpho-histological and Transcriptome Analysis Reveal the Unreduced Sperm Formation Mechanism in cdk1-Depletion Zebrafish.Marine biotechnology (New York, N.Y.) · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Lactation insufficiency affects many women worldwide. During lactation, a large portion of mammary gland alveolar cells become polyploid, but how these cells balance the hyperproliferation occurring during normal alveologenesis with terminal differentiation required for lactation is unknown. Here, we show that DNA damage accumulates due to replication stress during pregnancy, activating the DNA damage response. Modulation of DNA damage levels in vivo by intraductal injections of nucleosides or DNA damaging agents reveals that the degree of DNA damage accumulated during pregnancy governs endoreplication and milk production. We identify a mechanism involving early mitotic arrest through CDK1 inactivation, resulting in a heterogeneous alveolar population with regards to ploidy and nuclei number. The inactivation of CDK1 is mediated by the DNA damage response kinase WEE1 with homozygous loss of Wee1 resulting in decreased endoreplication, alveologenesis and milk production. Thus, we propose that the DNA damage response to replication stress couples proliferation and endoreplication during mammary gland alveologenesis. Our study sheds light on mechanisms governing lactogenesis and identifies non-hormonal means for increasing milk production.
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Registered trials
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.