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1.
BMC Plant Biol ; 24(1): 391, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38735929

RESUMO

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 F1 hybrid crosses and the chromsome numbers and compostions in T. turgidum-Ae. umbellulata F2 still not known. RESULTS: In this study, 11 T.turgidum-Ae. umbellulata triploid F1 hybrid crosses were produced by distant hybridization. All of the triploid F1 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 F2 seeds from the triploid F1 hybrid plants of 10 crosses (no F2 seeds for STU 16) varied from 35 to 43, and the proportions of euploid and aneuploid F2 plants were 49.61% and 50.39%, respectively. In the aneuploid F2 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 F2 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 F2 plants. Furthermore, polymorphic fluorescence in situ hybridization karyotypes for all the U chromosomes were also identified in the F2 plants when compared with the Ae. umbellulata parents. These results provide useful information for our understanding the naturally occurred T. turgidum-Ae. umbellulata amphidiploids.


Assuntos
Aegilops , Instabilidade Cromossômica , Cromossomos de Plantas , Hibridização Genética , Triticum , Triticum/genética , Cromossomos de Plantas/genética , Aegilops/genética , Meiose/genética , Triploidia , Poliploidia , Genoma de Planta
3.
Theor Appl Genet ; 137(6): 140, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780770

RESUMO

Greenbug [Schizaphis graminum (Rondani)] is a serious insect pest that not only damages cereal crops, but also transmits several destructive viruses. The emergence of new greenbug biotypes in the field makes it urgent to identify novel greenbug resistance genes in wheat. CWI 76364 (PI 703397), a synthetic hexaploid wheat (SHW) line, exhibits greenbug resistance. Evaluation of an F2:3 population from cross OK 14319 × CWI 76364 indicated that a dominant gene, designated Gb9, conditions greenbug resistance in CWI 76364. Selective genotyping of a subset of F2 plants with contrasting phenotypes by genotyping-by-sequencing identified 25 SNPs closely linked to Gb9 on chromosome arm 7DL. Ten of these SNPs were converted to Kompetitive allele-specific polymerase chain reaction (KASP) markers for genotyping the entire F2 population. Genetic analysis delimited Gb9 to a 0.6-Mb interval flanked by KASP markers located at 599,835,668 bp (Stars-KASP872) and 600,471,081 bp (Stars-KASP881) on 7DL. Gb9 was 0.5 cM distal to Stars-KASP872 and 0.5 cM proximal to Stars-KASP881. Allelism tests indicated that Gb9 is a new greenbug resistance gene which confers resistance to greenbug biotypes C, E, H, I, and TX1. TX1 is one of the most widely virulent biotypes and has overcome most known wheat greenbug resistance genes. The introgression of Gb9 into locally adapted wheat cultivars is of economic importance, and the KASP markers developed in this study can be used to tag Gb9 in cultivar development.


Assuntos
Afídeos , Genes de Plantas , Genótipo , Polimorfismo de Nucleotídeo Único , Poliploidia , Triticum , Triticum/genética , Animais , Afídeos/genética , Afídeos/fisiologia , Marcadores Genéticos , Mapeamento Cromossômico , Fenótipo , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Resistência à Doença/genética , Alelos , Melhoramento Vegetal
4.
J Cell Biol ; 223(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38727809

RESUMO

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.


Assuntos
Citocinese , Hepatócitos , Mitose , Organoides , Humanos , Hepatócitos/metabolismo , Organoides/citologia , Organoides/metabolismo , Poliploidia
5.
Nat Genet ; 56(5): 737, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38750321
6.
Proc Natl Acad Sci U S A ; 121(21): e2400018121, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38748576

RESUMO

Hybridization blurs species boundaries and leads to intertwined lineages resulting in reticulate evolution. Polyploidy, the outcome of whole genome duplication (WGD), has more recently been implicated in promoting and facilitating hybridization between polyploid species, potentially leading to adaptive introgression. However, because polyploid lineages are usually ephemeral states in the evolutionary history of life it is unclear whether WGD-potentiated hybridization has any appreciable effect on their diploid counterparts. Here, we develop a model of cytotype dynamics within mixed-ploidy populations to demonstrate that polyploidy can in fact serve as a bridge for gene flow between diploid lineages, where introgression is fully or partially hampered by the species barrier. Polyploid bridges emerge in the presence of triploid organisms, which despite critically low levels of fitness, can still allow the transfer of alleles between diploid states of independently evolving mixed-ploidy species. Notably, while marked genetic divergence prevents polyploid-mediated interspecific gene flow, we show that increased recombination rates can offset these evolutionary constraints, allowing a more efficient sorting of alleles at higher-ploidy levels before introgression into diploid gene pools. Additionally, we derive an analytical approximation for the rate of gene flow at the tetraploid level necessary to supersede introgression between diploids with nonzero introgression rates, which is especially relevant for plant species complexes, where interspecific gene flow is ubiquitous. Altogether, our results illustrate the potential impact of polyploid bridges on the (re)distribution of genetic material across ecological communities during evolution, representing a potential force behind reticulation.


Assuntos
Fluxo Gênico , Hibridização Genética , Modelos Genéticos , Poliploidia , Evolução Molecular , Diploide , Alelos
7.
J Transl Med ; 22(1): 441, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730481

RESUMO

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.


Assuntos
Morte Celular , Células Gigantes , Interfase , Microtúbulos , Poliploidia , Humanos , Interfase/efeitos dos fármacos , Microtúbulos/metabolismo , Microtúbulos/efeitos dos fármacos , Linhagem Celular Tumoral , Morte Celular/efeitos dos fármacos , Células Gigantes/efeitos dos fármacos , Células Gigantes/metabolismo , Células Gigantes/patologia , Dinâmica Mitocondrial/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Glioblastoma/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/genética , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/genética , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
8.
Int J Biol Macromol ; 268(Pt 1): 131706, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38643921

RESUMO

Various cancers frequently exhibit polyploidy, observed in a condition where a cell possesses more than two sets of chromosomes, which is considered a hallmark of the disease. The state of polyploidy often leads to aneuploidy, where cells possess an abnormal number or structure of chromosomes. Recent studies suggest that oncogenes contribute to aneuploidy. This finding significantly underscores its impact on cancer. Cancer cells exposed to certain chemotherapeutic drugs tend to exhibit an increased incidence of polyploidy. This occurrence is strongly associated with several challenges in cancer treatment, including metastasis, resistance to chemotherapy and the recurrence of malignant tumors. Indeed, it poses a significant hurdle to achieve complete tumor eradication and effective cancer therapy. Recently, there has been a growing interest in the field of polyploidy related to cancer for developing effective anti-cancer therapies. Polyploid cancer cells confer both advantages and disadvantages to tumor pathogenicity. This review delineates the diverse characteristics of polyploid cells, elucidates the pivotal role of polyploidy in cancer, and explores the advantages and disadvantages it imparts to cancer cells, along with the current approaches tried in lab settings to target polyploid cells. Additionally, it considers experimental strategies aimed at addressing the outstanding questions within the realm of polyploidy in relation to cancer.


Assuntos
Neoplasias , Poliploidia , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Aneuploidia , Animais
9.
Cell Rep Methods ; 4(5): 100754, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38614089

RESUMO

Precision medicine's emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given its combinatorial nature. While classical algorithms have made strides in addressing this issue, the potential of quantum computing remains largely untapped. Here, we present the vehicle routing problem (VRP) assembler: an approach that transforms this task into a vehicle routing problem, an optimization formulation solvable on a quantum computer. We demonstrate its potential and feasibility through a proof of concept on short synthetic diploid and triploid genomes using a D-Wave quantum annealer. To tackle larger-scale assembly problems, we integrate the VRP assembler with Google's OR-Tools, achieving a haplotype-resolved local assembly across the human major histocompatibility complex (MHC) region. Our results show encouraging performance compared to Hifiasm with phasing accuracy approaching the theoretical limit, underscoring the promising future of quantum computing in bioinformatics.


Assuntos
Diploide , Haplótipos , Poliploidia , Humanos , Haplótipos/genética , Biologia Computacional/métodos , Algoritmos , Teoria Quântica , Genoma Humano , Complexo Principal de Histocompatibilidade/genética
10.
Mol Phylogenet Evol ; 196: 108087, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677353

RESUMO

Polyploidy, or whole-genome duplication, is expected to confound the inference of species trees with phylogenetic methods for two reasons. First, the presence of retained duplicated genes requires the reconciliation of the inferred gene trees to a proposed species tree. Second, even if the analyses are restricted to shared single copy genes, the occurrence of reciprocal gene loss, where the surviving genes in different species are paralogs from the polyploidy rather than orthologs, will mean that such genes will not have evolved under the corresponding species tree and may not produce gene trees that allow inference of that species tree. Here we analyze three different ancient polyploidy events, using synteny-based inferences of orthology and paralogy to infer gene trees from nearly 17,000 sets of homologous genes. We find that the simple use of single copy genes from polyploid organisms provides reasonably robust phylogenetic signals, despite the presence of reciprocal gene losses. Such gene trees are also most often in accord with the inferred species relationships inferred from maximum likelihood models of gene loss after polyploidy: a completely distinct phylogenetic signal present in these genomes. As seen in other studies, however, we find that methods for inferring phylogenetic confidence yield high support values even in cases where the underlying data suggest meaningful conflict in the phylogenetic signals.


Assuntos
Modelos Genéticos , Filogenia , Poliploidia , Evolução Molecular , Sintenia , Funções Verossimilhança
11.
Cancer Lett ; 590: 216843, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38579893

RESUMO

Recurrent chemotherapy-induced senescence and resistance are attributed to the polyploidization of cancer cells that involve genomic instability and poor prognosis due to their unique form of cellular plasticity. Autophagy, a pre-dominant cell survival mechanism, is crucial during carcinogenesis and chemotherapeutic stress, favouring polyploidization. The selective autophagic degradation of essential proteins associated with cell cycle progression checkpoints deregulate mitosis fidelity and genomic integrity, imparting polyploidization of cancer cells. In connection with cytokinesis failure and endoreduplication, autophagy promotes the formation, maintenance, and generation of the progeny of polyploid giant cancer cells. The polyploid cancer cells embark on autophagy-guarded elevation in the expression of stem cell markers, along with triggered epithelial and mesenchymal transition and senescence. The senescent polyploid escapers represent a high autophagic index than the polyploid progeny, suggesting regaining autophagy induction and subsequent autophagic degradation, which is essential for escaping from senescence/polyploidy, leading to a higher proliferative phenotypic progeny. This review documents the various causes of polyploidy and its consequences in cancer with relevance to autophagy modulation and its targeting for therapeutic intervention as a novel therapeutic strategy for personalized and precision medicine.


Assuntos
Autofagia , Senescência Celular , Neoplasias , Células-Tronco Neoplásicas , Poliploidia , Humanos , Senescência Celular/efeitos dos fármacos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Transição Epitelial-Mesenquimal
12.
Proc Natl Acad Sci U S A ; 121(15): e2313921121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38568968

RESUMO

Malvaceae comprise some 4,225 species in 243 genera and nine subfamilies and include economically important species, such as cacao, cotton, durian, and jute, with cotton an important model system for studying the domestication of polyploids. Here, we use chromosome-level genome assemblies from representatives of five or six subfamilies (depending on the placement of Ochroma) to differentiate coexisting subgenomes and their evolution during the family's deep history. The results reveal that the allohexaploid Helicteroideae partially derive from an allotetraploid Sterculioideae and also form a component of the allodecaploid Bombacoideae and Malvoideae. The ancestral Malvaceae karyotype consists of 11 protochromosomes. Four subfamilies share a unique reciprocal chromosome translocation, and two other subfamilies share a chromosome fusion. DNA alignments of single-copy nuclear genes do not yield the same relationships as inferred from chromosome structural traits, probably because of genes originating from different ancestral subgenomes. These results illustrate how chromosome-structural data can unravel the evolutionary history of groups with ancient hybrid genomes.


Assuntos
Genoma de Planta , Gossypium , Genoma de Planta/genética , Gossypium/genética , Genômica/métodos , Poliploidia , Cariótipo , Evolução Molecular
13.
Sci Rep ; 14(1): 7892, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570611

RESUMO

Haplotype-resolved genome assembly plays a crucial role in understanding allele-specific functions. However, obtaining haplotype-resolved assembly for auto-polyploid genomes remains challenging. Existing methods can be classified into reference-based phasing, assembly-based phasing, and gamete binning. Nevertheless, there is a lack of cost-effective and efficient methods for haplotyping auto-polyploid genomes. In this study, we propose a novel phasing algorithm called PolyGH, which combines Hi-C and gametic data. We conducted experiments on tetraploid potato cultivars and divided the method into three steps. Firstly, gametic data was utilized to bin non-collapsed contigs, followed by merging adjacent fragments of the same type within the same contig. Secondly, accurate Hi-C signals related to differential genomic regions were acquired using unique k-mers. Finally, collapsed fragments were assigned to haplotigs based on combined Hi-C and gametic signals. Comparing PolyGH with Hi-C-based and gametic data-based methods, we found that PolyGH exhibited superior performance in haplotyping auto-polyploid genomes when integrating both data types. This approach has the potential to enhance haplotype-resolved assembly for auto-polyploid genomes.


Assuntos
Células Germinativas , Poliploidia , Humanos , Análise de Sequência de DNA/métodos , Haplótipos/genética , Alelos
14.
Int J Mol Sci ; 25(8)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38673782

RESUMO

Mesenchymal stem cells (MSC) attract an increasing amount of attention due to their unique therapeutic properties. Yet, MSC can undergo undesirable genetic and epigenetic changes during their propagation in vitro. In this study, we investigated whether polyploidy can compromise MSC oncological safety and therapeutic properties. For this purpose, we compared the impact of polyploidy on the transcriptome of cancer cells and MSC of various origins (bone marrow, placenta, and heart). First, we identified genes that are consistently ploidy-induced or ploidy-repressed through all comparisons. Then, we selected the master regulators using the protein interaction enrichment analysis (PIEA). The obtained ploidy-related gene signatures were verified using the data gained from polyploid and diploid populations of early cardiomyocytes (CARD) originating from iPSC. The multistep bioinformatic analysis applied to the cancer cells, MSC, and CARD indicated that polyploidy plays a pivotal role in driving the cell into hypertranscription. It was evident from the upregulation of gene modules implicated in housekeeping functions, stemness, unicellularity, DNA repair, and chromatin opening by means of histone acetylation operating via DNA damage associated with the NUA4/TIP60 complex. These features were complemented by the activation of the pathways implicated in centrosome maintenance and ciliogenesis and by the impairment of the pathways related to apoptosis, the circadian clock, and immunity. Overall, our findings suggest that, although polyploidy does not induce oncologic transformation of MSC, it might compromise their therapeutic properties because of global epigenetic changes and alterations in fundamental biological processes. The obtained results can contribute to the development and implementation of approaches enhancing the therapeutic properties of MSC by removing polyploid cells from the cell population.


Assuntos
Apoptose , Células-Tronco Mesenquimais , Poliploidia , Transcriptoma , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Humanos , Apoptose/genética , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Cílios/metabolismo , Cílios/genética , Simulação por Computador , Feminino , Perfilação da Expressão Gênica , Epigênese Genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Biologia Computacional/métodos
15.
Mol Biol Rep ; 51(1): 582, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678168

RESUMO

BACKGROUND: Hybridization associated with polyploidy studies is rare in the tropics. The genus Zygopetalum (Orchidaceae) was investigated here as a case study of Neotropical plants. In the rocky highlands of the Ibitipoca State Park (ISP), southeast Brazil, individuals with intermediate colors and forms between the species Z. maculatum and Z. triste were commonly identified. METHODS AND RESULTS: Chromosomal analysis and DNA quantity showed a uniform population. Regardless of the aspects related to the color and shape of floral structures, all individuals showed 2n = 96 chromosomes and an average of 14.05 pg of DNA. Irregularities in meiosis associated with chromosome number and C value suggest the occurrence of polyploidy. The genetic distance estimated using ISSR molecular markers revealed the existence of genetic variability not related to morphological clusters. Morphometric measurements of the flower pieces revealed that Z. maculatum shows higher variation than Z. triste although lacking a defined circumscription. CONCLUSION: The observed variation can be explained by the polyploid and phenotypic plasticity resulting from the interaction of the genotypes with the heterogeneous environments observed in this habitat.


Assuntos
Variação Genética , Orchidaceae , Fenótipo , Poliploidia , Orchidaceae/genética , Variação Genética/genética , Brasil , Cromossomos de Plantas/genética , Genótipo , Flores/genética , Flores/anatomia & histologia , Repetições de Microssatélites/genética , Hibridização Genética/genética
17.
Bioinformatics ; 40(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38632086

RESUMO

MOTIVATION: Major improvements in sequencing technologies and genome sequence assembly have led to a huge increase in the number of available genome sequences. In turn, these genome sequences form an invaluable source for evolutionary, ecological, and comparative studies. One kind of analysis that has become routine is the search for traces of ancient polyploidy, particularly for plant genomes, where whole-genome duplication (WGD) is rampant. RESULTS: Here, we present a major update of a previously developed tool wgd, namely wgd v2, to look for remnants of ancient polyploidy, or WGD. We implemented novel and improved previously developed tools to (a) construct KS age distributions for the whole-paranome (collection of all duplicated genes in a genome), (b) unravel intragenomic and intergenomic collinearity resulting from WGDs, (c) fit mixture models to age distributions of gene duplicates, (d) correct substitution rate variation for phylogenetic placement of WGDs, and (e) date ancient WGDs via phylogenetic dating of WGD-retained gene duplicates. The applicability and feasibility of wgd v2 for the identification and the relative and absolute dating of ancient WGDs is demonstrated using different plant genomes. AVAILABILITY AND IMPLEMENTATION: wgd v2 is open source and available at https://github.com/heche-psb/wgd.


Assuntos
Duplicação Gênica , Genoma de Planta , Filogenia , Poliploidia , Evolução Molecular , Software , Genômica/métodos
18.
Trends Ecol Evol ; 39(5): 424-426, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521739

RESUMO

Cold temperatures have been posited as a key driver of polyploidy (possession of multiple chromosome sets). However, high temperatures associated with fire, and the indirect impact of post-fire environments in polypoid formation and establishment deserve more attention for a comprehensive understanding of polyploid ecology, evolution, and current distributions.


Assuntos
Incêndios , Poliploidia , Evolução Biológica , Temperatura Baixa
19.
J Biol Chem ; 300(4): 107136, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38447798

RESUMO

Polyploid giant cancer cells (PGCC) are frequently detected in tumors and are increasingly recognized for their roles in chromosomal instability and associated genome evolution that leads to cancer recurrence. We previously reported that therapy stress promotes polyploidy, and that acid ceramidase plays a role in depolyploidization. In this study, we used an RNA-seq approach to gain a better understanding of the underlying transcriptomic changes that occur as cancer cells progress through polyploidization and depolyploidization. Our results revealed gene signatures that are associated with disease-free and/or overall survival in several cancers and identified the cell cycle inhibitor CDKN1A/p21 as the major hub in PGCC and early progeny. Increased expression of p21 in PGCC was limited to the cytoplasm. We previously demonstrated that the sphingolipid enzyme acid ceramidase is dispensable for polyploidization upon therapy stress but plays a crucial role in depolyploidization. The current study demonstrates that treatment of cells with ceramide is not sufficient for p53-independent induction of p21 and that knockdown of acid ceramidase, which hydrolyzes ceramide, does not interfere with upregulation of p21. In contrast, blocking the expression of p21 with UC2288 prevented the induction of acid ceramidase and inhibited both the formation of PGCC from parental cells as well as the generation of progeny from PGCC. Taken together, our data suggest that p21 functions upstream of acid ceramidase and plays an important role in polyploidization and depolyploidization.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21 , Células Gigantes , Neoplasias , Poliploidia , Humanos , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células Gigantes/metabolismo , Células Gigantes/patologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Transcriptoma
20.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542284

RESUMO

Climate change, particularly drought stress, significantly impacts plant growth and development, necessitating the development of resilient crops. This study investigated physiological and molecular modulations to drought stress between diploid parent species and their polyploid progeny in the Brassica species. While no significant phenotypic differences were observed among the six species, drought stress reduced growth parameters by 2.4% and increased oxidative stress markers by 1.4-fold. Drought also triggered the expression of genes related to stress responses and led to the accumulation of specific metabolites. We also conducted the first study of perfluorooctane sulfonic acid (PFOS) levels in leaves as a drought indicator. Lower levels of PFOS accumulation were linked to plants taking in less water under drought conditions. Both diploid and polyploid species responded to drought stress similarly, but there was a wide range of variation in their responses. In particular, responses were less variable in polyploid species than in diploid species. This suggests that their additional genomic components acquired through polyploidy may improve their flexibility to modulate stress responses. Despite the hybrid vigor common in polyploid species, Brassica polyploids demonstrated intermediate responses to drought stress. Overall, this study lays the framework for future omics-level research, including transcriptome and proteomic studies, to deepen our understanding of drought tolerance mechanisms in Brassica species.


Assuntos
Brassica , Brassica/genética , Estresse Fisiológico/genética , Secas , Proteômica , Poliploidia
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