ArticleProceedings of the National Academy of Sciences of the United States of America2017
A p53-dependent response limits the viability of mammalian haploid cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 85 citations in OpenAlex.
- Metabolic Imbalance Triggers Adaptive Remodeling to Accelerate Diploidization in Murine Haploid Embryonic Stem Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial metabolic imbalance drives diploidization in mouse haploid embryonic stem cells via NADPH overload.Nature communications · 2026Article
- Balanced DNA-to-cytoplasm ratio at the 2-cell stage is critical for mouse preimplantation development.iScience · 2026Article
- Insulated piggyBac and FRT vectors for engineering transgenic homozygous and heterozygous eHAP cells.Biology open · 2025Article
- Fragility of ER homeostatic regulation underlies haploid instability in human somatic cells.The Journal of biological chemistry · 2024Article
- Haploidy-linked cell proliferation defects limit larval growth in zebrafish.Open biology · 2024Article
- Genetic Screening of Haploid Neural Stem Cells Reveals that Nfkbia and Atp2b4 are Key Regulators of Oxidative Stress in Neural Precursors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Overexpression of Let-7a mitigates diploidization in mouse androgenetic haploid embryonic stem cells.iScience · 2024Article
- Intrinsic deletion at 10q23.31, including theLife science alliance · 2024Article
- BCL2 is a major regulator of haploidy maintenance in murine embryonic stem cells.Cell proliferation · 2023Article
- Transcriptome profiles and chromatin states in mouse androgenetic haploid embryonic stem cells.Cell proliferation · 2023Article
- Proton and alpha radiation-induced mutational profiles in human cells.Scientific reports · 2023Article
- Integrated multi-omics analyses reveal homology-directed repair pathway as a unique dependency in near-haploid leukemia.Blood cancer journal · 2023Article
- Development of a Cellular Model Mimicking Specific HDAC Inhibitors.Methods in molecular biology (Clifton, N.J.) · 2023Article
- HAP1, a new revolutionary cell model for gene editing using CRISPR-Cas9.Frontiers in cell and developmental biology · 2023Review
- Whole-Genome Doubling as a source of cancer: how, when, where, and why?Frontiers in cell and developmental biology · 2023Review
- Chromosomal instability (CIN) in HAP1 cell lines revealed by multiplex fluorescence in situ hybridisation (M-FISH).Molecular cytogenetics · 2022Article
- Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.Genome research · 2022Article
- Review
- The P5-type ATPase ATP13A1 modulates major histocompatibility complex I-related protein 1 (MR1)-mediated antigen presentation.The Journal of biological chemistry · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The recent development of haploid cell lines has facilitated forward genetic screenings in mammalian cells. These lines include near-haploid human cell lines isolated from a patient with chronic myelogenous leukemia (KBM7 and HAP1), as well as haploid embryonic stem cells derived from several organisms. In all cases, haploidy was shown to be an unstable state, so that cultures of mammalian haploid cells rapidly become enriched in diploids. Here we show that the observed diploidization is due to a proliferative disadvantage of haploid cells compared with diploid cells. Accordingly, single-cell-sorted haploid mammalian cells maintain the haploid state for prolonged periods, owing to the absence of competing diploids. Although the duration of interphase is similar in haploid and diploid cells, haploid cells spend longer in mitosis, indicative of problems in chromosome segregation. In agreement with this, a substantial proportion of the haploids die at or shortly after the last mitosis through activation of a p53-dependent cytotoxic response. Finally, we show that p53 deletion stabilizes haploidy in human HAP1 cells and haploid mouse embryonic stem cells. We propose that, similar to aneuploidy or tetraploidy, haploidy triggers a p53-dependent response that limits the fitness of mammalian cells.
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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.