ArticleNature cell biology2015
Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3 null mice.
Article in Nature cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- mTOR inhibition abrogates human mammary stem cells and early breast cancer progression markers.Breast cancer research : BCR · 2023Article
- Abnormal B-cell development in TIMP-deficient bone marrow.Blood advances · 2021Article
- Progesterone receptor-DNA methylation crosstalk regulates depletion of uterine leiomyoma stem cells: A potential therapeutic target.Stem cell reports · 2021Article
- Protein signatures of centenarians and their offspring suggest centenarians age slower than other humans.Aging cell · 2021Article
- Targeting DNA Methylation Depletes Uterine Leiomyoma Stem Cell-enriched Population by Stimulating Their Differentiation.Endocrinology · 2020Article
- Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth.The Journal of cell biology · 2019Article
- Mammary stem cells and progenitors: targeting the roots of breast cancer for prevention.The EMBO journal · 2019Review
- Identifying the murine mammary cell target of metformin exposure.Communications biology · 2019Article
- Plasma proteomic signature of age in healthy humans.Aging cell · 2018Article
- Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.The Journal of cell biology · 2018Article
- p16 loss rescues functional decline of Brca1-deficient mammary stem cells.Cell cycle (Georgetown, Tex.) · 2017Article
- Cellular mechano-environment regulates the mammary circadian clock.Nature communications · 2017Article
- TIMPs: versatile extracellular regulators in cancer.Nature reviews. Cancer · 2017Review
- Molecular mechanisms of asymmetric divisions in mammary stem cells.EMBO reports · 2016Review
- Aging is associated with an expansion of CD49fAging · 2016Article
- A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.Cell stem cell · 2016Article
- Breast Cancer beyond the Age of Mutation.Gerontology · 2016Article
- The mammary stem cell hierarchy: a looking glass into heterogeneous breast cancer landscapes.Endocrine-related cancer · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Age is the primary risk factor for breast cancer in women. Bipotent basal stem cells actively maintain the adult mammary ductal tree, but with age tissues atrophy. We show that cell-extrinsic factors maintain the adult stem cell pool during ageing and dictate tissue stoichiometry. Mammary stem cells spontaneously expand more than 11-fold in virgin adult female mice lacking specific genes for TIMPs, the natural metalloproteinase inhibitors. Compound Timp1/Timp3 null glands exhibit Notch activation and accelerated gestational differentiation. Proteomics of mutant basal cells uncover altered cytoskeletal and extracellular protein repertoires, and we identify aberrant mitotic spindle orientation in these glands, a process that instructs asymmetric cell division and fate. We find that progenitor activity normally declines with age, but enriched stem/progenitor pools prevent tissue regression in Timp mutant mammary glands without affecting carcinogen-induced cancer susceptibility. Thus, improved stem cell content can extend mouse mammary tissue lifespan without altering cancer risk in this mouse model.
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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.