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BMC Plant Biology May 2024Unreduced gamete formation during meiosis plays a critical role in natural polyploidization. However, the unreduced gamete formation mechanisms in Triticum...
BACKGROUND
Unreduced gamete formation during meiosis plays a critical role in natural polyploidization. However, the unreduced gamete formation mechanisms in Triticum turgidum-Aegilops umbellulata triploid F hybrid crosses and the chromsome numbers and compostions in T. turgidum-Ae. umbellulata F still not known.
RESULTS
In this study, 11 T.turgidum-Ae. umbellulata triploid F hybrid crosses were produced by distant hybridization. All of the triploid F hybrids had 21 chromosomes and two basic pathways of meiotic restitution, namely first-division restitution (FDR) and single-division meiosis (SDM). Only FDR was found in six of the 11 crosses, while both FDR and SDM occurred in the remaining five crosses. The chromosome numbers in the 127 selfed F seeds from the triploid F hybrid plants of 10 crosses (no F seeds for STU 16) varied from 35 to 43, and the proportions of euploid and aneuploid F plants were 49.61% and 50.39%, respectively. In the aneuploid F plants, the frequency of chromosome loss/gain varied among genomes. The chromosome loss of the U genome was the highest (26.77%) among the three genomes, followed by that of the B (22.83%) and A (11.81%) genomes, and the chromosome gain for the A, B, and U genomes was 3.94%, 3.94%, and 1.57%, respectively. Of the 21 chromosomes, 7U (16.54%), 5 A (3.94%), and 1B (9.45%) had the highest loss frequency among the U, A, and B genomes. In addition to chromosome loss, seven chromosomes, namely 1 A, 3 A, 5 A, 6 A, 1B, 1U, and 6U, were gained in the aneuploids.
CONCLUSION
In the aneuploid F plants, the frequency of chromosome loss/gain varied among genomes, chromsomes, and crosses. In addition to variations in chromosome numbers, three types of chromosome translocations including 3UL·2AS, 6UL·1AL, and 4US·6AL were identified in the F plants. Furthermore, polymorphic fluorescence in situ hybridization karyotypes for all the U chromosomes were also identified in the F plants when compared with the Ae. umbellulata parents. These results provide useful information for our understanding the naturally occurred T. turgidum-Ae. umbellulata amphidiploids.
Topics: Chromosomal Instability; Hybridization, Genetic; Triticum; Chromosomes, Plant; Aegilops; Meiosis; Triploidy; Polyploidy; Genome, Plant
PubMed: 38735929
DOI: 10.1186/s12870-024-05110-8 -
Leukemia Jun 2024
Topics: Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Trisomy; Chromosomes, Human, Pair 6; Genomics; Prognosis; Multiomics
PubMed: 38734787
DOI: 10.1038/s41375-024-02268-w -
Stem Cell Research Jun 2024Y chromosome deletion and karyotype abnormalities are commonly associated with congenital non-obstructive azoospermia, impairing spermatogenesis. Specifically, the...
Y chromosome deletion and karyotype abnormalities are commonly associated with congenital non-obstructive azoospermia, impairing spermatogenesis. Specifically, the deletion of the Y chromosome Azoospermia factor a (AZFa) has been identified in infertile males with severely impaired spermatogenesis. AZFa, encompassing megabase-scale of the Y chromosome region, poses challenges in modeling AZFa deletion-related male infertility using gene editing tools. Here, we successfully created an AZFa-deleted human embryonic stem cell line utilizing the CRISPR/Cas9 gene editing tool. Our analysis indicates the AZFa-deleted stem cell line holds promise for differentiation into ectoderm, mesoderm, and endoderm, highlighting its potential for further comprehensive study.
Topics: Humans; Human Embryonic Stem Cells; Male; Cell Line; Chromosomes, Human, Y; Cell Differentiation; CRISPR-Cas Systems; Chromosome Deletion; Gene Editing
PubMed: 38733811
DOI: 10.1016/j.scr.2024.103436 -
International Journal of Molecular... Apr 2024High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms...
High malignancy is a prominent characteristic of epithelial ovarian cancer (EOC), emphasizing the necessity for further elucidation of the potential mechanisms underlying cancer progression. Aneuploidy and copy number variation (CNV) partially contribute to the heightened malignancy observed in EOC; however, the precise features of aneuploidy and their underlying molecular patterns, as well as the relationship between CNV and aneuploidy in EOC, remain unclear. In this study, we employed single-cell sequencing data along with The Cancer Genome Atlas (TCGA) to investigate aneuploidy and CNV in EOC. The technique of fluorescence in situ hybridization (FISH) was employed using specific probes. The copy number variation within the genomic region of chromosome 8 (42754568-47889815) was assessed and utilized as a representative measure for the ploidy status of individual cells in chromosome 8. Differential expression analysis was performed between different subgroups based on chromosome 8 ploidy. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and hub-gene analyses were subsequently utilized to identify crucial genes involved. By classifying enriched tumor cells into distinct subtypes based on chromosome 8 ploidy combined with TCGA data integration, we identified key genes driving chromosome 8 aneuploidy in EOC, revealing that gene involvement through the mediated non-homologous end-joining pathway may play a pivotal role in disease progression. Further validation through analysis of the GEO and TCGA database and survival assessment, considering both mRNA expression levels and CNV status of , has confirmed its involvement in the progression of EOC. Further functional analysis revealed an upregulation of in both ovarian EOC cells and tissues, with its expression showing a significant correlation with the extent of copy number variation (CNV) on chromosome 8. Taken together, CNV amplification and aneuploidy of chromosome 8 are important characteristics of EOC. and the mediated NHEJ pathway may play a crucial role in driving aneuploidy on chromosome 8 during the progression of EOC.
Topics: Female; Humans; Aneuploidy; Carcinoma, Ovarian Epithelial; Chromosomes, Human, Pair 8; Disease Progression; DNA Copy Number Variations; Gene Expression Regulation, Neoplastic; In Situ Hybridization, Fluorescence; Ovarian Neoplasms
PubMed: 38732044
DOI: 10.3390/ijms25094825 -
Journal of Translational Medicine May 2024Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells...
Microtubule targeting agents (MTAs) are commonly prescribed to treat cancers and predominantly kill cancer cells in mitosis. Significantly, some MTA-treated cancer cells escape death in mitosis, exit mitosis and become malignant polyploid giant cancer cells (PGCC). Considering the low number of cancer cells undergoing mitosis in tumor tissues, killing them in interphase may represent a favored antitumor approach. We discovered that ST-401, a mild inhibitor of microtubule (MT) assembly, preferentially kills cancer cells in interphase as opposed to mitosis, a cell death mechanism that avoids the development of PGCC. Single cell RNA sequencing identified mRNA transcripts regulated by ST-401, including mRNAs involved in ribosome and mitochondrial functions. Accordingly, ST-401 induces a transient integrated stress response, reduces energy metabolism, and promotes mitochondria fission. This cell response may underly death in interphase and avoid the development of PGCC. Considering that ST-401 is a brain-penetrant MTA, we validated these results in glioblastoma cell lines and found that ST-401 also reduces energy metabolism and promotes mitochondria fission in GBM sensitive lines. Thus, brain-penetrant mild inhibitors of MT assembly, such as ST-401, that induce death in interphase through a previously unanticipated antitumor mechanism represent a potentially transformative new class of therapeutics for the treatment of GBM.
Topics: Humans; Interphase; Microtubules; Polyploidy; Cell Line, Tumor; Cell Death; Giant Cells; Mitochondrial Dynamics; Energy Metabolism; Glioblastoma; Neoplasms; Mitochondria; Gene Expression Regulation, Neoplastic
PubMed: 38730481
DOI: 10.1186/s12967-024-05234-3 -
Journal of Neurodevelopmental Disorders May 2024Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures....
BACKGROUND
Phelan-McDermid syndrome (PMS) is a genetic neurodevelopmental disorder caused by SHANK3 haploinsufficiency and is associated with an increased risk for seizures. Previous literature indicates that around one third of individuals with PMS also have epilepsy or seizures, with a wide range of types and ages of onset. Investigating the impact of seizures on intellectual and adaptive functioning for PMS is a primary concern for caregivers and is important to understanding the natural history of this syndrome.
METHODS
We report on results from 98 individuals enrolled in a prospective, longitudinal study. We detailed seizure frequency, type, and age of onset, and we analyzed seizure occurrence with best estimate IQ, adaptive functioning, clinical features, and genotype. We conducted multiple linear regression analyses to assess the relationship between the presence of seizures and the Vineland Adaptive Behavior Scale, Second Edition (VABS-II) Adaptive Behavior Composite score and the best estimate full-scale IQ. We also performed Chi-square tests to explore associations between seizure prevalence and genetic groupings. Finally, we performed Chi-square tests and t-tests to explore the relationship between seizures and demographic features, features that manifest in infancy, and medical features.
RESULTS
Seizures were present in 41% of the cohort, and age of onset was widely variable. The presence of seizures was associated with significantly lower adaptive and intellectual functioning. Genotype-phenotype analyses were discrepant, with no differences in seizure prevalence across genetic classes, but with more genes included in deletions of participants with 22q13 deletions and seizures compared to those with 22q13 deletions and no seizures. No clinical associations were found between the presence of seizures and sex, history of pre- or neonatal complications, early infancy, or medical features. In this cohort, generalized seizures were associated with developmental regression, which is a top concern for PMS caregivers.
CONCLUSIONS
These results begin to eludicate correlates of seizures in individuals with PMS and highlight the importance of early seizure management. Importantly, presence of seizures was associated with adaptive and cognitive functioning. A larger cohort might be able to identify additional associations with medical features. Genetic findings suggest an increased capability to realize genotype-phenotype relationships when deletion size is taken into account.
Topics: Humans; Male; Female; Seizures; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 22; Child; Child, Preschool; Adolescent; Longitudinal Studies; Young Adult; Adult; Prospective Studies; Infant; Nerve Tissue Proteins
PubMed: 38730350
DOI: 10.1186/s11689-024-09541-0 -
The Journal of Cell Biology Aug 2024Binucleated polyploid cells are common in many animal tissues, where they arise by endomitosis, a non-canonical cell cycle in which cells enter M phase but do not...
Binucleated polyploid cells are common in many animal tissues, where they arise by endomitosis, a non-canonical cell cycle in which cells enter M phase but do not undergo cytokinesis. Different steps of cytokinesis have been shown to be inhibited during endomitosis M phase in rodents, but it is currently unknown how human cells undergo endomitosis. In this study, we use fetal-derived human hepatocyte organoids (Hep-Orgs) to investigate how human hepatocytes initiate and execute endomitosis. We find that cells in endomitosis M phase have normal mitotic timings, but lose membrane anchorage to the midbody during cytokinesis, which is associated with the loss of four cortical anchoring proteins, RacGAP1, Anillin, SEPT9, and citron kinase (CIT-K). Moreover, reduction of WNT activity increases the percentage of binucleated cells in Hep-Orgs, an effect that is dependent on the atypical E2F proteins, E2F7 and E2F8. Together, we have elucidated how hepatocytes undergo endomitosis in human Hep-Orgs, providing new insights into the mechanisms of endomitosis in mammals.
Topics: Humans; Cytokinesis; Hepatocytes; Mitosis; Organoids; Polyploidy
PubMed: 38727809
DOI: 10.1083/jcb.202403020 -
Royal Society Open Science May 2024Improving the salt stress tolerance of crops is an important goal in plant breeding. Changes in the number of chromosome sets (i.e. ploidy level) cause genome dosage...
Improving the salt stress tolerance of crops is an important goal in plant breeding. Changes in the number of chromosome sets (i.e. ploidy level) cause genome dosage effects which can result in enhanced or novel traits. Maternal inheritance versus paternal inheritance of the same chromosome sets can have differential epigenetic effects on traits of F1 offspring. Hence, genome dosage effects can be parent-of-origin independent or dependent. The model plant displays both genome dosage and parent-of-origin effects on plant growth under non-stress conditions. Using an isogenic ploidy series of diploid, triploid and tetraploid lines, we investigate the extent of genome dosage effects and their parent-of-origin dependency on salt stress tolerance of seedlings across 10 different accessions (genetic backgrounds). We detected genome dosage effects on salt stress tolerance for tetraploid lines in five accessions. In addition, through the generation of isogenic reciprocal F1 triploid lines, both parent-of-origin dependent and independent genome dosage effects on salt stress tolerance were detected. Thus, our results indicate not only that genome dosage balance effects can have significant impacts on abiotic stress tolerance in but also that parent-of-origin specific genome dosage effects can affect salt stress tolerance in plants.
PubMed: 38721127
DOI: 10.1098/rsos.231766 -
Scientific Data May 2024Decoding complex plant omics is essential for advancing our understanding of plant biology, evolution, and breeding as well as for practical applications in agriculture,...
Decoding complex plant omics is essential for advancing our understanding of plant biology, evolution, and breeding as well as for practical applications in agriculture, conservation, and biotechnology. The advent of Next-Generation Sequencing (NGS) has revolutionized global plant genomic research, offering high-throughput, cost-effective, and accurate methods for generating genomic data. However, challenges still exist that suggest an entirely unresolved genome characterized by high heterozygosity, extensive repetitive sequences, and complex ploidy features. In addition, individual investigation of genomic information from various genetic resources is essential for omics research, as there are differences in traits within a single breed beyond a species due to the uniqueness of sequence variation. This article provides high-quality genomic and transcriptomic insights targeted at the agronomical background.
Topics: Genome, Plant; Genomics; High-Throughput Nucleotide Sequencing; Information Dissemination; Plant Breeding; Plants
PubMed: 38719829
DOI: 10.1038/s41597-024-03305-0 -
Clinical Epigenetics May 2024Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal...
BACKGROUND
Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty.
METHODS
An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR.
RESULTS
The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission.
CONCLUSION
We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.
Topics: Humans; Calcium-Binding Proteins; DNA Methylation; Chromosomes, Human, Pair 14; Intercellular Signaling Peptides and Proteins; Genomic Imprinting; Membrane Proteins; Child; Male; Comparative Genomic Hybridization; Female; Chromosome Deletion; Child, Preschool; Phenotype; Abnormalities, Multiple; Imprinting Disorders; Muscle Hypotonia; Facies
PubMed: 38715103
DOI: 10.1186/s13148-024-01652-8