Biology subjects

Yamamoto, T.

Publications and source records attributed to Yamamoto, T..

125 records · Page 7Linked to original sources

bioRxiv2019

A method to determine the double bond position in unsaturated fatty acids by solvent plasmatization using liquid chromatography-mass spectrometry

Fatty acids (FAs) are the central components of life: they constitute biological membranes in the form of lipid, act as signaling molecules, and are used as energy sources. FAs are classified according to their chain lengths and the number and position of carbon-carbon double bond, and their physiological character is largely defined by these structural properties. Determination of the precise structural properties is crucial for characterizing FAs, but pinpointing the exact position of carbon-carbon double bond in FA molecules is challenging. Herein, a new analytical method is reported for determining the double bond position of mono- and poly-unsaturated FAs using liquid chromatography-mass spectrometry (LC-MS) coupled with solvent plasmatization. With the aid of plasma on ESI capirally, epoxidation or peroxidation of carbon-carbon double bond in FAs is facilitated. Subsequently, molecular fragmentation occurs at or beside the epoxidized or peroxidized double bond via collision-induced dissociation (CID), and the position of the double bond is elucidated. In this method, FAs are separated by LC, modified by plasma, fragmented via CID, and detected using a time-of-flight mass spectrometer in a seamless manner such that the FA composition in a mixture can be determined. Our method enables thorough characterization of FA species with distinguishing multiple isomers, and therefore can uncover the true diversity of FAs for their application in food, health, and medical sciences.

biochemistry↗

bioRxiv2019

Transmission network reconstruction for foot-and-mouth disease outbreaks incorporating farm-level covariates

Transmission network modelling to infer who infected whom in infectious disease outbreaks is a highly active area of research. Outbreaks of foot-and-mouth disease have been a key focus of transmission network models that integrate genomic and epidemiological data. The aim of this study was to extend Laus systematic Bayesian inference framework to incorporate additional parameters representing predominant species and numbers of animals held on a farm.\n\nLaus Bayesian Markov chain Monte Carlo algorithm was reformulated, verified and pseudo-validated on simulated outbreaks populated with demographic data Japan and Australia. The modified model was then implemented on genomic and epidemiological data from the 2010 outbreak of foot-and-mouth disease in Japan, and outputs compared to those from the SCOTTI model implemented in BEAST2.\n\nThe modified model achieved improvements in overall accuracy when tested on the simulated outbreaks. When implemented on the actual outbreak data from Japan, infected farms that held predominantly pigs were estimated to have five times the transmissibility of infected cattle farms and be 49% less susceptible. The farm-level incubation period was 1 day shorter than the latent period, the timing of the seeding of the outbreak in Japan was inferred, as were key linkages between clusters and features of farms involved in widespread dissemination of this outbreak. To improve accessibility the modified model has been implemented as the R package BORIS for use in future outbreaks.

microbiology↗

bioRxiv2019

Aggressive periodontitis with neutropenia caused by MMD2 mutation

Aggressive periodontitis causes rapid periodontal tissue destruction and is a disease that occurs at a young age and runs in the patients family. Here, we revealed a heterozygous A116V missense mutation in the gene encoding monocyte to macrophage differentiation associated 2 (MMD2) protein in a Japanese family with aggressive periodontitis and neutropenia. Analyses of patients peripheral blood revealed a low number of neutrophils but abundant quantity of CD34+ hematopoietic stem and progenitor cells (HSPCs). Moreover, mutant Mmd2 mice showed severe alveolar bone loss and neutropenia. In patients and mutant Mmd2 mice, differentiation of HSPCs into granulocytes was also impeded, and their granulocytes were functionally impaired. Taken together, A116V mutation in MMD2 gene induced mild neutropenia and slightly limited the immune defense response. Our studies suggested that aggressive periodontitis in association with A116V MMD2 mutation constitutes a new immune system defect that belongs to the same spectrum of severe congenital neutropenia.

genomics↗

bioRxiv2019

A reciprocal inhibition model of alternations between non-dissociative and dissociative states in patients with PTSD

ObjectiveTraumatic life-events can leave individuals with contrasting posttraumatic stress disorder (PTSD) symptoms, including re-experiencing and avoidance. Notably, patients with PTSD are known to periodically switch between two opposing attentional biases; namely, toward threat and away from threat. We hypothesized that reciprocal inhibition between the amygdala and ventromedial prefrontal cortex (vmPFC) may induce alternations between these attentional biases, which in turn may contribute to the re-experiencing and avoidance symptoms, respectively.\n\nMethodsTo test this reciprocal inhibition model, we performed an experiment to measure the attentional biases of patients with PTSD. We examined the differential relationships between PTSD symptom clusters (re-experiencing/avoidance) and attentional biases (toward/away from threat). Additionally, we performed a meta-regression analysis to examine the role of amygdala reactivity in the imbalance between re-experiencing and avoidance symptoms.\n\nResultsWe found that attentional bias toward threat was selectively associated with re-experiencing symptoms whereas attentional bias away from threat was selectively associated with avoidance symptoms. Meta-regression analysis based on twelve participant populations (total N = 316) revealed that left amygdala activity was positively correlated with the severity of re-experiencing symptoms relative to avoidance symptoms.\n\nConclusionsOur findings support the hypothesis that reciprocal inhibition of common neural circuits may underlie the switch between attentional biases toward and away from threat as well as that between re-experiencing and avoidance symptoms. Re-experiencing and avoidance/emotional numbing are the core symptoms used to distinguish between the non-dissociative and dissociative PTSD subtypes. The reciprocal inhibition mechanism may help elucidate the mechanisms underlying those PTSD subtypes.

neuroscience↗

bioRxiv2019

Cloning of Two Gene Clusters Involved in the Catabolism of 2,4-Dinitrophenol by Paraburkholderia sp. Strain KU-46 and Characterization of the Initial DnpAB Enzymes and a Two-Component Monooxygenase DnpC1C2

Besides an industrial pollutant, 2,4-dinitrophenol (DNP) has been used illegally as a weight loss drug that had claimed human lives. Little is known about the metabolism of DNP, particularly among Gram-negative bacteria. In this study, two non-contiguous genetic loci of Paraburkholderia (formerly Burkholderia) sp. strain KU-46 genome were identified and four key initial genes (dnpA, dnpB, and dnpC1C2) were characterized to provide molecular and biochemical evidence for the degradation of DNP via the formation of 4-nitrophenol (NP), a pathway that is unique among DNP utilizing bacteria. Reverse transcription PCR analysis indicated that the dnpA gene encoding the initial hydride transferase (28 kDa), and the dnpB gene encoding a nitrite-eliminating enzyme (33 kDa), are inducible by DNP and the two genes are organized in an operon. Purified DnpA and DnpB from overexpression clones in Escherichia coli effected the transformation of DNP to NP via the formation of hydride-Meisenheimer complex of DNP. The function of DnpB appears new since all homologs of DnpB sequences in the protein database are annotated as putative nitrate ABC transporter substrate-binding proteins. The gene cluster responsible for the degradation of DNP after NP formation was designated dnpC1C2DXFER. DnpC1 and DnpC2 were functionally characterized as the respective FAD reductase and oxygenase components of the two-component NP monooxygenase. Both NP and 4-nitrocatechol were shown to be substrates, producing hydroquinone and hydroxyquinol, respectively. Elucidation of the hqdA1A2BCD gene cluster allows the delineation of the final degradation pathway of hydroquinone to {beta}-ketoadipate prior to its entry to the tricarboxylic acid cycle.\n\nImportanceThis study fills a gap in our knowledge and understanding of the genetic basis and biochemical pathway for the degradation of 2,4-dinitrophenol (DNP) in Gram-negative bacteria, represented by the prototypical Paraburkholderia sp. strain KU-46 that metabolizes DNP through the formation of 4-nitrophenol, a pathway unseen by other DNP utilizers. The newly cloned genes could serve as DNA probes in biomonitoring as well as finding application in new biocatalyst development to access green chemicals. By and large, knowledge of the diverse strategies used by microorganisms to degrade DNP will contribute to the development of bioremediation solutions since DNP is an industrial pollutant used widely in the chemical industry for the synthesis of pesticides, insecticides, sulfur dyes, wood preservatives, and explosives, etc. (119 words)

microbiology↗

bioRxiv2019

De novo whole-genome assembly in interspecific hybrid table grape, ‘Shine Muscat’

This study presents the first genome sequence of an interspecific grape hybrid, Shine Muscat (Vitis labruscana x V. vinifera), an elite table grape cultivar bred in Japan. The complexity of the genome structure, arising from the interspecific hybridization, necessitated the use of a sophisticated genome assembly pipeline with short-read genome sequence data. The resultant genome assemblies consisted of two types of sequences: a haplotype-phased sequence of the highly heterozygous genomes and an unphased sequence representing a \"haploid\" genome. The unphased sequences spanned 490.1 Mb in length, 99.4% of the estimated genome size, with 8,696 scaffold sequences with an N50 length of 13.2 Mb. The phased sequences had 15,650 scaffolds spanning 1.0 Gb with N50 of 4.2 Mb. The two sequences comprised 94.7% and 96.3% of the core eukaryotic genes, indicating that the entire genome of Shine Muscat was represented. Examination of genome structures revealed possible genome rearrangements between the genomes of Shine Muscat and a V. vinifera line. Furthermore, full-length transcriptome sequencing analysis revealed 13,947 gene loci on the Shine Muscat genome, from which 26,199 transcript isoforms were transcribed. These genome resources provide new insights that could help cultivation and breeding strategies produce more high-quality table grapes such as Shine Muscat.

genomics↗

bioRxiv2019

Genome-wide analysis of transcriptional bursting-induced noise in mammalian cells

Transcriptional bursting is stochastic activation and inactivation of promoters, leading to discontinuous production of mRNA, and is considered to be a contributing factor to cell-to-cell heterogeneity in gene expression. However, it remains elusive how the kinetic properties of transcriptional bursting (e.g., burst size, burst frequency, and noise induced by transcriptional bursting) are regulated in mammalian cells. In this study, we performed a genome-wide analysis of transcriptional bursting in mouse embryonic stem cells (mESCs) using single-cell RNA-sequencing. We found that the kinetics of transcriptional bursting was determined by a combination of promoter and gene body binding proteins, including polycomb repressive complex 2 and transcription elongation-related factors. Furthermore, large-scale CRISPR-Cas9-based screening and functional analysis revealed that the Akt/MAPK signaling pathway regulated bursting kinetics by modulating transcription elongation efficiency. These results uncover key molecular mechanisms underlying transcriptional bursting and cell-to-cell gene expression noise in mammalian cells.

systems biology↗

bioRxiv2019

Field evaluation of a quantitative, and rapid malaria diagnostic system using a fluorescent Blue-ray optical device

We improved a previously developed quantitative malaria diagnostic system based on fluorescent Blue-ray optical device. Here, we first improved the diagnostic system to enable fully automated operation and the field application was evaluated in Kenya. We detected Plasmodium falciparum in blood samples collected from 288 individuals aged 1-16 years using nested polymerase chain reaction (nPCR), rapid diagnostic test (RDT), and automated system. Compared to RDT, the automated system exhibited a higher sensitivity (100%; 95% confidence interval [CI], 93.3-100%) and specificity (92.8%; 95%CI, 88.5-95.8%). The limit of detection was 0.0061%. Linear regression analysis revealed a correlation between the automated system and microscopic examination for detecting parasitemia (adjusted R2 value=0.63, P=1.13x10-12). The automated system exhibited a stable quantification of parasitemia and a higher diagnostic accuracy for parasitemia than RDT. This indicates the potential of this system as a valid alternative to conventional methods used at local health facilities, which lack basic infrastructure.

physiology↗

bioRxiv2019

Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1G93A Mouse Model for ALS

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which motor neurons degenerate resulting in muscle atrophy, paralysis and fatality. Studies using mouse models of ALS indicate a protracted period of disease development with progressive motor neuron pathology, evident as early as embryonic and postnatal stages. Key missing information includes concomitant alterations in the sensorimotor circuit essential for normal development and function of the neuromuscular system. Leveraging unique brainstem circuitry, we show in vitro evidence for reflex circuit-specific postnatal abnormalities in the jaw proprioceptive sensory neurons in the well-studied SOD1G93A mouse. These include impaired and arrhythmic action potential burst discharge associated with a deficit in Nav1.6 Na+ channels. However, the mechanoreceptive and nociceptive trigeminal ganglion neurons and the visual sensory retinal ganglion neurons were resistant to excitability changes in age matched SOD1G93A mice. Computational modeling of the observed disruption in sensory patterns predicted asynchronous self-sustained motor neuron discharge suggestive of imminent reflexive defects such as muscle fasciculations in ALS. These results demonstrate a novel reflex circuit-specific proprioceptive sensory abnormality in ALS.\n\nSignificance StatementNeurodegenerative diseases have prolonged periods of disease development and progression. Identifying early markers of vulnerability can therefore help devise better diagnostic and treatment strategies. In this study, we examined postnatal abnormalities in the electrical excitability of muscle spindle afferent proprioceptive neurons in the well-studied SOD1G93A mouse model for neurodegenerative motor neuron disease, ALS. Our findings suggest that these proprioceptive sensory neurons are exclusively afflicted early in the disease process relative to sensory neurons of other modalities. Moreover, they presented Nav1.6 Na+ channel deficiency which contributed to arrhythmic burst discharge. Such sensory arrhythmia could initiate reflexive defects such as muscle fasciculations in ALS as suggested by our computational model.

neuroscience↗

bioRxiv2019

miR-26a regulates extracellular vesicle secretion from prostate cancer cells via targeting SHC4, PFDN4 and CHORDC1

Extracellular vesicles (EVs) are known to be involved in intercellular communication during cancer progression; thus, elucidating the detailed mechanism will contribute to the development of a novel strategy for EV-targeted cancer treatment. However, the biogenesis of EVs in cancer cells is not completely understood. MicroRNAs (miRNAs) regulate a variety of physiological and pathological phenomena; thus, miRNAs could regulate EV secretion. Here, we performed high-throughput miRNA-based screening to identify the regulators of EV secretion using an ExoScreen assay. By using this miRNA-based screening, we identified miR-26a, which was reported as a tumor suppressive miRNA, as a miRNA involved in EV secretion from prostate cancer (PCa) cells. In addition, we found that the SHC4, PFDN4, and CHORDC1 genes regulate EV secretion in PCa cells. Suppression of these genes by siRNAs significantly inhibited the secretion of EVs in PCa cells. Furthermore, the progression of PCa cells was inhibited in an in vivo study. On the other hand, injection of EVs isolated from PCa cells partially rescued this suppressive effect on tumor growth. Taken together, our findings suggest that miR-26a regulates EV secretion via targeting SHC4, PFDN4, and CHORDC1 in PCa cells, resulting in the suppression of PCa progression.

cancer biology↗

bioRxiv2019

Human recombinant erythropoietin improves motor function in rats with spinal cord compression myelopathy

OBJECTIVEErythropoietin (EPO) is a clinically available hematopoietic cytokine. The aim of this study was to evaluate the effect of EPO on a rat model of cervical cord compression myelopathy and to explore the possibility of its use as a pharmacological treatment.\n\nMETHODSTo produce the chronic cervical cord compression model, thin polyurethane sheets were implanted under the C5-C6 laminae of rats and gradually expanded due to water absorption. In this model, motor functions significantly declined from 7 weeks after surgery. Based on the result, EPO administration was started 8 weeks after surgery. Motor function as seen with rotarod performance and grip strength was measured 16 weeks after surgery, and then motor neurons were stained with H-E and NeuN staining, and counted. Apoptotic cell death was assessed with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. To assess transfer of EPO into spinal cord tissue, the EPO level in spinal cord tissue was measured with an enzyme-linked immunosorbent assay for each group after subcutaneous injection of EPO.\n\nRESULTSHigh-dose EPO (5000 IU/kg) administered from 8 weeks after surgery markedly restored and maintained motor function in the Compression groups (P < 0.01). EPO significantly prevented loss of motor neurons in the anterior horn (P < 0.05) and significantly decreased the number of TUNEL-positive apoptotic cells (P < 0.05). The EPO level in spinal cord tissue was significantly higher in the High-dose EPO group than other groups.\n\nCONCLUSIONSEPO improves motor function in rats with progressive chronic compression myelopathy. EPO protects anterior horn motor neurons and inhibits neuronal cell apoptosis in spinal cord compression. The neuroprotective effects can be produced through transfer of EPO into spinal cord tissue. These findings suggest that EPO has high potential as a treatment for developing compression myelopathy.

neuroscience↗

bioRxiv2019

Modeling the Human Segmentation Clock with Pluripotent Stem Cells

Pluripotent stem cells (PSCs) have increasingly been used to model different aspects of embryogenesis and organ formation1. Despite recent advances in the in vitro induction of major mesodermal lineages and mesoderm-derived cell types2,3, experimental model systems that can recapitulate more complex biological features of human mesoderm development and patterning are largely missing. Here, we utilized induced pluripotent stem cells (iPSCs) for the stepwise in vitro induction of presomitic mesoderm (PSM) and its derivatives to model distinct aspects of human somitogenesis. We focused initially on modeling the human segmentation clock, a major biological concept believed to underlie the rhythmic and controlled emergence of somites, which give rise to the segmental pattern of the vertebrate axial skeleton. We succeeded to observe oscillatory expression of core segmentation clock genes, including HES7 and DKK1, and identified novel oscillatory genes in human iPSC-derived PSM. We furthermore determined the period of the human segmentation clock to be around five hours and showed the presence of dynamic traveling wave-like gene expression within in vitro induced human PSM. Utilizing CRISPR/Cas9-based genome editing technology, we then targeted genes, for which mutations in patients with abnormal axial skeletal development such as spondylocostal dysostosis (SCD) (HES7, LFNG and DLL3) or spondylothoracic dysostosis (STD) (MESP2) have been reported. Subsequent analysis of patient-like iPSC knock-out lines as well as patient-derived iPSCs together with their genetically corrected isogenic controls revealed gene-specific alterations in oscillation, synchronization or differentiation properties, validating the overall utility of our model system, to recapitulate not only key features of human somitogenesis but also to provide novel insights into diseases associated with the formation and patterning of the human axial skeleton.

developmental biology↗

bioRxiv2019

Targeting of RBM10 to S1-1 Nuclear Bodies: Targeting Sequences and its Biological Significance

RBM10 is an RNA-binding protein that regulates alternative splicing (AS). It localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs) in the nucleus. We investigated the biological significance of this localization in relation to its molecular function. Our analyses, employing deletion mutants, revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs act synergistically to localize RBM10 to S1-1 NBs. The C2H2 ZnF not only acts as an NBTS, but is also essential for AS regulation by RBM10. Moreover, RBM10 does not participate in S1-1 NB formation, and without alterations of RBM10 protein levels, its NB-localization changes, increasing as cellular transcriptional activity declines, and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in NBs via its NBTSs when cellular transcription decreases. We propose that the C2H2 ZnF exerts its NB-targeting activity when RBM10 is unbound by pre-mRNAs, and that NB-localization of RBM10 is a mechanism to control its AS activity in the nucleus. Note that the previous title of this manuscript was Targeting of RBM10 to S1-1 Nuclear Bodies: Targeting Sequences and its Biological Significance.

molecular biology↗

bioRxiv2018

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis

There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from saliva on the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques. We investigated the general and oral conditions from each patient and performed next-generation sequencing analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the saliva were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that in saliva present on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results indicated that oral bacteria did not affect the formation of atheromatous plaques directly. However, the metabolic products of microbiome or the host inflammatory response might indirectly influence the composition of atheromatous plaques.

microbiology↗

bioRxiv2018

Effect of continuous compressive force on the expression of RANKL, OPG, and VEGF in MC3T3-E1 and MLO-Y4 cells

Osteocytes, known to have mechano-sensory functions, influence the regulation of bone remodeling. However, the mechanism by which osteocytes regulate bone metabolism when mechanical forces are being applied is still unclear. Osteoclastogenesis is mainly regulated by receptor activator of nuclear factor kappa-B ligand (RANKL); the protein osteoprotegerin (OPG) and angiogenesis also play important roles in osteogenesis. RANKL, OPG, and vascular endothelial growth factor (VEGF) are thought to be key factors for bone metabolism. In this study, we examined the effect of a continuous compressive force (CF) on the expression of RANKL, OPG, and VEGF in osteoblastic murine osteocytes (MLO-Y4) and osteoblastic (MC3T3-E1) cells. Gene and protein expression levels of RANKL, OPG, and VEGF in MLO-Y4 and MC3T3-E1 cells were quantitatively determined by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Both cell types were also subjected to a CF of 1.0 g/cm2 for 1, 3, 6, and 12 hours. Furthermore, the effect of a stretch-activated (S-A) channel was examined by gadolinium (Gd3+) administration. The ratio of gene and protein expressions of RANKL, VEGF, and RANKL/OPG in MLO-Y4 cells were significantly higher than in MC3T3-E1 cells, while the expression of OPG was significantly lower. After CF application, both cell types showed significant increases in RANKL and VEGF expression as well as the RANKL/OPG ratio. Additionally, the upregulated gene and protein levels of these factors were reduced by Gd3+ administration.\n\nThese findings suggest that osteocytes play more important roles in bone metabolism and angiogenesis than osteoblasts. Osteocytes regulate the expression of RANKL, OPG, and VEGF via the S-A channel through the response to mechanical stress.

cell biology↗

bioRxiv2018

Does the Diffusion Tensor Model Predict the Neurite Distribution of Cerebral Cortical Gray Matter? - Cortical DTI-NODDI

Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) are widely used models to infer microstructural features in the brain from diffusion-weighted MRI. Several studies have recently applied both models to increase sensitivity to biological changes, however, it remains uncertain how these measures are associated. Here we show that cortical distributions of DTI and NODDI are associated depending on the choice of b-value, a factor reflecting strength of diffusion weighting gradient. We analyzed a combination of high, intermediate and low b-value data of multi-shell diffusion-weighted MRI (dMRI) in healthy 456 subjects of the Human Connectome Project using NODDI, DTI and a mathematical conversion from DTI to NODDI. Cortical distributions of DTI and DTI-derived NODDI metrics were remarkably associated with those in NODDI, particularly when applied highly diffusion-weighted data (b-value =3000 sec/mm2). This was supported by simulation analysis, which revealed that DTI-derived parameters with lower b-value datasets suffered from errors due to heterogeneity of cerebrospinal fluid fraction and partial volume. These findings suggest that high b-value DTI redundantly parallels with NODDI-based cortical neurite measures, but the conventional low b-value DTI does not reasonably characterize cortical microarchitecture.

neuroscience↗

bioRxiv2017

Uncoordinated centrosome duplication cycle underlies the instability of non-diploid states in mammalian somatic cells

In animals, somatic cells are usually diploid and are unstable when haploid for unknown reasons. In this study, by comparing isogenic human cell lines with different ploidies, we found frequent centrosome loss specifically in the haploid state, which profoundly contributed to haploid instability through monopolar spindle formation and subsequent mitotic defects. We also found that efficiency of centriole licensing and duplication, but not that of DNA replication, changes proportionally to ploidy level, causing gradual loss or frequent overduplication of centrioles in haploid and tetraploid cells, respectively. Centriole licensing efficiency seemed to be modulated by astral microtubules, whose development scaled with ploidy level, and artificial enhancement of aster formation in haploid cells restored centriole licensing efficiency to diploid levels. Haploid-specific centrosome loss was also observed in parthenogenetic mouse embryos. We propose that incompatibility between the centrosome duplication and DNA replication cycles arising from different scaling properties of these bioprocesses upon ploidy changes, underlies the instability of non-diploid somatic cells in mammals.\n\nSummaryYaguchi et al. show that a delay or acceleration of centriole licensing compromises the control of centrosome number in haploid or tetraploid human cells, respectively, suggesting a cellular basis of the instability of non-diploid somatic cells in mammals.

cell biology↗