ArticleProceedings of the National Academy of Sciences of the United States of America2013
Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.Cancer research communications · 2023Article
- Escape from Cellular Senescence Is Associated with Chromosomal Instability in Oral Pre-Malignancy.Biology · 2023Review
- Chromosomal Instability Characterizes Pediatric Medulloblastoma but Is Not Tolerated in the Developing Cerebellum.International journal of molecular sciences · 2022Article
- Effects of aneuploidy on cell behaviour and function.Nature reviews. Molecular cell biology · 2022Review
- Review
- Acute systemic loss of Mad2 leads to intestinal atrophy in adult mice.Scientific reports · 2021Article
- Premature aging syndrome showing random chromosome number instabilities with CDC20 mutation.Aging cell · 2020Article
- Review
- Degree and site of chromosomal instability define its oncogenic potential.Nature communications · 2020Article
- Altering microtubule dynamics is synergistically toxic with spindle assembly checkpoint inhibition.Life science alliance · 2020Article
- Targeting MAD2 modulates stemness and tumorigenesis in human Gastric Cancer cell lines.Theranostics · 2020Article
- Tissue stem cells: the new actors in the aneuploidy field.Cell cycle (Georgetown, Tex.) · 2019Article
- Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint.Cell reports · 2018Article
- The p38α Stress Kinase Suppresses Aneuploidy Tolerance by Inhibiting Hif-1α.Cell reports · 2018Article
- Chromosome integrity checkpoints in stem and progenitor cells: transitions upon differentiation, pathogenesis, and aging.Cellular and molecular life sciences : CMLS · 2018Review
- Deletion of theeLife · 2017Article
- Living in CIN: Mitotic Infidelity and Its Consequences for Tumor Promotion and Suppression.Developmental cell · 2016Review
- Aneuploidy in stem cells.World journal of stem cells · 2016Review
- Article
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Authors and funding
10 authors at 6 institutions in 5 countries.
Funding
Abstract
The spindle assembly checkpoint (SAC) ensures correct chromosome segregation during mitosis by preventing aneuploidy, an event that is detrimental to the fitness and survival of normal cells but oncogenic in tumor cells. Deletion of SAC genes is incompatible with early mouse development, and RNAi-mediated depletion of SAC components in cultured cells results in rapid death. Here we describe the use of a conditional KO of mouse Mad2, an essential component of the SAC signaling cascade, as a means to selectively induce chromosome instability and aneuploidy in the epidermis of the skin. We observe that SAC inactivation is tolerated by interfollicular epidermal cells but results in depletion of hair follicle bulge stem cells. Eventually, a histologically normal epidermis develops within ∼1 mo after birth, albeit without any hair. Mad2-deficient cells in this epidermis exhibited abnormal transcription of metabolic genes, consistent with aneuploid cell state. Hair follicle bulge stem cells were completely absent, despite the continued presence of rudimentary hair follicles. These data demonstrate that different cell lineages within a single tissue respond differently to chromosome instability: some proliferating cell lineages can survive, but stem cells are highly sensitive.
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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.