Diploid radiation despite massive polyploidization
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ABSTRACT:
PROVIDER: PRJEB31511 | ENA |
REPOSITORIES: ENA
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Project description:A defining feature of the mammalian liver is polyploidy, a numerical change in the entire complement of chromosomes. The first step of polyploidization involves cell division with failed cytokinesis. Although polyploidy is common, affecting ~90% of hepatocytes in mice and 50% in humans, the specialized role played by polyploid cells in liver homeostasis and disease remains poorly understood. The goal of this study was to identify novel signals that regulate polyploidization, and we focused on microRNAs (miRNAs). First, to test whether miRNAs could regulate hepatic polyploidy we examined livers from Dicer1 liver-specific knockout mice, which are devoid of mature miRNAs. Loss of miRNAs resulted in a 3-fold reduction in binucleate hepatocytes, indicating that miRNAs regulate polyploidization. Secondly, we surveyed age-dependent expression of miRNAs in wild-type mice and identified a subset of miRNAs, including miR-122, that is differentially expressed at 2-3 weeks, a period when extensive polyploidization occurs. Next, we examined Mir122 knockout mice and observed profound, life-long depletion of polyploid hepatocytes, proving that miR-122 is required for complete hepatic polyploidization. Moreover, the polyploidy defect in Mir122 knockout mice was ameliorated by adenovirus-mediated over-expression of miR-122, underscoring the critical role miR-122 plays in polyploidization. Finally, we identified direct targets of miR-122 (Cux1, Rhoa, Iqgap1, Mapre1, Nedd4l and Slc25a34) that regulate cytokinesis. Inhibition of each target induced cytokinesis failure and promoted hepatic binucleation. Conclusion: Our data demonstrate that miR-122 is both necessary and sufficient in liver polyploidization. Among the different signals that have been associated with hepatic polyploidy, miR-122 is the first liver-specific signal identified. These studies will serve as the foundation for future work investigating miR-122 in liver maturation, homeostasis and disease. Livers from C57Bl/6 mice were isolated at defined ages: embryonic day 15.5 (n=3; mixed gender), 2 weeks (n=3; male), 3 weeks (n=3, male) and 7 weeks (n=3; male). Differential miRNA expression was assessed using the nCounter Mouse miRNA Expression Assay Kit (nanoString).
2016-03-29 | E-GEOD-68537 | biostudies-arrayexpress
Project description:A defining feature of the mammalian liver is polyploidy, a numerical change in the entire complement of chromosomes. The first step of polyploidization involves cell division with failed cytokinesis. Although polyploidy is common, affecting ~90% of hepatocytes in mice and 50% in humans, the specialized role played by polyploid cells in liver homeostasis and disease remains poorly understood. The goal of this study was to identify novel signals that regulate polyploidization, and we focused on microRNAs (miRNAs). First, to test whether miRNAs could regulate hepatic polyploidy we examined livers from Dicer1 liver-specific knockout mice, which are devoid of mature miRNAs. Loss of miRNAs resulted in a 3-fold reduction in binucleate hepatocytes, indicating that miRNAs regulate polyploidization. Secondly, we surveyed age-dependent expression of miRNAs in wild-type mice and identified a subset of miRNAs, including miR-122, that is differentially expressed at 2-3 weeks, a period when extensive polyploidization occurs. Next, we examined Mir122 knockout mice and observed profound, life-long depletion of polyploid hepatocytes, proving that miR-122 is required for complete hepatic polyploidization. Moreover, the polyploidy defect in Mir122 knockout mice was ameliorated by adenovirus-mediated over-expression of miR-122, underscoring the critical role miR-122 plays in polyploidization. Finally, we identified direct targets of miR-122 (Cux1, Rhoa, Iqgap1, Mapre1, Nedd4l and Slc25a34) that regulate cytokinesis. Inhibition of each target induced cytokinesis failure and promoted hepatic binucleation. Conclusion: Our data demonstrate that miR-122 is both necessary and sufficient in liver polyploidization. Among the different signals that have been associated with hepatic polyploidy, miR-122 is the first liver-specific signal identified. These studies will serve as the foundation for future work investigating miR-122 in liver maturation, homeostasis and disease.
2016-03-29 | GSE68537 | GEO
Project description:Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.
2011-09-26 | GSE25985 | GEO
Project description:Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events. Tumor DNA was hybridized onto Illumina Human Omni-Quad v1.0 BeadChip or Human CNV370-Quad v3.0 BeadChip (Illumina, San Diego, CA, USA), following standard protocols supplied by the manufacturer. Data were extracted from the GenomeStudio software (Illumina), and subsequently normalized and segmented using thresholded quantile normalization (tQN) and BAFsegmentation, respectively (Staaf et al. Normalization of array-CGH data: influence of copy number imbalances. BMC Genomics 2007, 8:382; Staaf et al. Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays. Genome Biol 2008, 9:R136). Base pair positions are indicated according to the NCBI build 36 (hg18).
2011-09-25 | E-GEOD-25985 | biostudies-arrayexpress
Project description:In order to study the effect of polyploidization on gene expression in the leaves of Eucalyptus urophylla, triploid obtained by sexual polyploidization and its diploid control were used as materials, and leaves at different growth stages of different ploidies were collected for transcriptome sequencing.
2022-07-13 | GSE207860 | GEO
Project description:The TEL2, TTI1, and TTI2 proteins are co-chaperones for heat shock protein 90 (HSP90) to regulate the protein folding and maturation of phosphatidylinositol 3-kinase-related kinases (PIKKs). Referred to as the TTT complex, the genes that encode them are highly conserved from man to maize. TTT complex and PIKK genes exist mostly as single copy genes in organisms where they have been characterized. Members of this interacting protein network in maize were identified and synteny analyses were performed to study their evolution. Similar to other species, there is only one copy of each of these genes in maize which was due to a loss of the duplicated copy created by ancient allotetraploidy. Moreover, the retained copies of the TTT complex and the PIKK genes tolerated extensive retrotransposon insertion in their introns that resulted in increased gene lengths and gene body methylation, without apparent effect in normal gene expression and function. The results raise an interesting question on whether the reversion to single copy was due to selection against deleterious unbalanced gene duplications between members of the complex as predicted by the gene balance hypothesis, or due to neutral loss of extra copies. Uneven alteration of dosage either by adding extra copies or modulating gene expression of complex members is being proposed as a means to investigate whether the data supports the gene balance hypothesis or not.
| S-EPMC5681926 | biostudies-literature
Project description:We found that PTC undergo polyploidization immediately after AKI induced by ischemia. To identify the mechanism controlling polyploidization of PTC, we generated single-cell RNA sequencing (scRNAseq) datasets from healthy mouse kidneys, 2 and 30 days after ischemia reperfusion injury. We found that polyploid PTC become hypertrophic and undergo polyploidization in a YAP1-related manner. In particular, YAP1 controls polyploidization of PTC via E2f7, E2f8 and Akt1. We confirmed these findings by knocking-down those genes in vitro.
2022-10-01 | GSE212273 | GEO
Project description:Polyploidization as the consequence of 2n gamete formation is a prominent mechanism in plant evolution. Studying its effects on the genome and its expression has both basic and applied interest. We crossed two diploid (2n=2x=16) M. sativa plants, a subsp. falcata seed parent and a coerulea x falcata pollen parent that produce a mixture of n and 2n eggs and pollen, respectively. Such cross produced full-sib diploid and tetraploid (2n=4x=32) progenies, the latter being the result of bilateral sexual polyploidization (BSP). These unique materials allowed us to investigate the effects of BSP, and separating the effect of intraspecific hybridization from those of polyploidization by comparing 2x with 4x full sib progeny plants. SSR marker segregation demonstrated tetrasomic inheritance for all chromosomes but one, demonstrating that these neotetraploids are true autotetraploids. BSP brought about increased biomass, earlier flowering, higher seed set and weight, larger leaves with larger cells. Microarray analyses with M. truncatula gene chips showed that several hundred genes, related to diverse metabolic functions, changed their expression level as a consequence of polyploidization. In addition, cytosine methylation increased in 2x but not in 4x hybrids. Our results indicate that sexual polyploidization induce significant transcriptional novelty, possibly mediated in part by DNA methylation, and phenotypic novelty that can be at the base of improved adaptation and reproductive success of tetraploid M. sativa with respect to its diploid progenitor. These polyploidy-induced changes may have promoted the adoption of tetraploid alfalfa in agriculture.
2016-02-17 | GSE71559 | GEO
Project description:Polyploidization as the consequence of 2n gamete formation is a prominent mechanism in plant evolution. Studying its effects on the genome and its expression has both basic and applied interest. We crossed two diploid (2n=2x=16) M. sativa plants, a subsp. falcata seed parent and a coerulea x falcata pollen parent that produce a mixture of n and 2n eggs and pollen, respectively. Such cross produced full-sib diploid and tetraploid (2n=4x=32) progenies, the latter being the result of bilateral sexual polyploidization (BSP). These unique materials allowed us to investigate the effects of BSP, and separating the effect of intraspecific hybridization from those of polyploidization by comparing 2x with 4x full sib progeny plants. SSR marker segregation demonstrated tetrasomic inheritance for all chromosomes but one, demonstrating that these neotetraploids are true autotetraploids. BSP brought about increased biomass, earlier flowering, higher seed set and weight, larger leaves with larger cells. Microarray analyses with M. truncatula gene chips showed that several hundred genes, related to diverse metabolic functions, changed their expression level as a consequence of polyploidization. In addition, cytosine methylation increased in 2x but not in 4x hybrids. Our results indicate that sexual polyploidization induce significant transcriptional novelty, possibly mediated in part by DNA methylation, and phenotypic novelty that can be at the base of improved adaptation and reproductive success of tetraploid M. sativa with respect to its diploid progenitor. These polyploidy-induced changes may have promoted the adoption of tetraploid alfalfa in agriculture. Gene expression analysis of leaves at the vegetative stage of two Medicago sativa genotypes (PG-F9 and 12P) compared with three F1 diploid lines and three F1 tetraploid lines originating from crossing PG-F9 x 12P. Three biological replicates were taken for each sample, resulting in a total of twenty-four samples.
2016-02-17 | E-GEOD-71559 | biostudies-arrayexpress
Project description:Tumor cell radioresistance is a major challenge in radiotherapy. By contrast, radiation response heterogeneity of tumor cells is poorly understood. Here, we performed scRNA-seq and scATAC-seq of 6 Gy γ-ray treated human lung adenocarcinoma cells to dissect cellular radiation response heterogeneity from perspective of transcriptional and regulatory cell states. Notably, we observed heterogeneous radioresponsiveness in purified lung adenocarcinoma cells by qualified cellular radiation response based on transcriptional landscape. There was DNA repair and apoptosis related transcriptional cell state appeared post-irradiation. We identified gene markers in this radiation-associated cell state and screened promising targets for LUAD radiosensitization based on 107 transcriptomic data of radiotherapy treated LUAD patients from TCGA database. Besides, transcriptional cell states transition was obvious accompanied with radiation-induced cell cycle arrest in which cell-cell communication was a potential regulatory mechanism. Finally, we identified radiation-associated regulatory cell state and analyzed the regulatory network of key transcriptional factors in cellular radiation response.
2022-08-22 | GSE211617 | GEO