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Developmental Dynamics : An Official... Jan 2024Cardiovascular disease is a leading cause of death worldwide. Due to the limited proliferative and regenerative capacity of adult cardiomyocytes, the lost myocardium is... (Review)
Review
Cardiovascular disease is a leading cause of death worldwide. Due to the limited proliferative and regenerative capacity of adult cardiomyocytes, the lost myocardium is not replenished efficiently and is replaced by a fibrotic scar, which eventually leads to heart failure. Current therapies to cure or delay the progression of heart failure are limited; hence, there is a pressing need for regenerative approaches to support the failing heart. Cardiomyocytes undergo a series of transcriptional, structural, and metabolic changes after birth (collectively termed maturation), which is critical for their contractile function but limits the regenerative capacity of the heart. In regenerative organisms, cardiomyocytes revert from their terminally differentiated state into a less mature state (ie, dedifferentiation) to allow for proliferation and regeneration to occur. Importantly, stimulating adult cardiomyocyte dedifferentiation has been shown to promote morphological and functional improvement after myocardial infarction, further highlighting the importance of cardiomyocyte dedifferentiation in heart regeneration. Here, we review several hallmarks of cardiomyocyte maturation, and summarize how their reversal facilitates cardiomyocyte proliferation and heart regeneration. A detailed understanding of how cardiomyocyte dedifferentiation is regulated will provide insights into therapeutic options to promote cardiomyocyte de-maturation and proliferation, and ultimately heart regeneration in mammals.
Topics: Animals; Adult; Humans; Myocytes, Cardiac; Regeneration; Heart; Myocardium; Heart Failure; Cell Proliferation; Mammals
PubMed: 36502296
DOI: 10.1002/dvdy.557 -
Life (Basel, Switzerland) Sep 2023Legumes play a significant role in the alleviation of food insecurity, maintaining soil fertility, and achieving sustainable crop production under adverse environmental... (Review)
Review
Legumes play a significant role in the alleviation of food insecurity, maintaining soil fertility, and achieving sustainable crop production under adverse environmental conditions. The increased demand in legume production contemplates that attention on the genetic improvement of these crops through various means such as genetic engineering and mutation breeding should take a centre stage in global agriculture. Therefore, this paper provides a succinct analysis of the currently available literature on morphological and physiological traits in polyploidised leguminous plants to counter the adverse effects of drought stress. The effects of colchicine on various morphological and physiological traits of polyploidised legumes compared to their diploid counterparts were examined. Numerous reports revealed variations in these traits, such as improved root and shoot growth, plant biomass, chloroplastidic content, protein, RNA, and DNA. The differences observed were also associated with the strong relationship between plant ploidy induction and colchicine application. Furthermore, the analysis indicated that polyploidisation remains dose-dependent and may be achievable within a shorter space of time as this antimitotic chemical interferes with chromosome separations in somatic plant cells. The efficiency of this process also depends on the advancement of treatment conditions (in vitro, in vivo, or ex vitro) and the successful regeneration of polyploidised plants for adaptation under drought stress conditions. As such, the improvement in metabolite profile and other essential growth characteristics serves as a clear indication that induced polyploidy needs to be further explored to confer resilience to environmental stress and improve crop yield under drought stress conditions in leguminous plants.
PubMed: 37895348
DOI: 10.3390/life13101966 -
BMC Biology Jul 2023Pennisetum giganteum (AABB, 2n = 4x = 28) is a C4 plant in the genus Pennisetum with origin in Africa but currently also grown in Asia and America. It is a...
BACKGROUND
Pennisetum giganteum (AABB, 2n = 4x = 28) is a C4 plant in the genus Pennisetum with origin in Africa but currently also grown in Asia and America. It is a crucial forage and potential energy grass with significant advantages in yield, stress resistance, and environmental adaptation. However, the mechanisms underlying these advantageous traits remain largely unexplored. Here, we present a high-quality genome assembly of the allotetraploid P. giganteum aiming at providing insights into biomass accumulation.
RESULTS
Our assembly has a genome size 2.03 Gb and contig N50 of 88.47 Mb that was further divided into A and B subgenomes. Genome evolution analysis revealed the evolutionary relationships across the Panicoideae subfamily lineages and identified numerous genome rearrangements that had occurred in P. giganteum. Comparative genomic analysis showed functional differentiation between the subgenomes. Transcriptome analysis found no subgenome dominance at the overall gene expression level; however, differentially expressed homoeologous genes and homoeolog-specific expressed genes between the two subgenomes were identified, suggesting that complementary effects between the A and B subgenomes contributed to biomass accumulation of P. giganteum. Besides, C4 photosynthesis-related genes were significantly expanded in P. giganteum and their sequences and expression patterns were highly conserved between the two subgenomes, implying that both subgenomes contributed greatly and almost equally to the highly efficient C4 photosynthesis in P. giganteum. We also identified key candidate genes in the C4 photosynthesis pathway that showed sustained high expression across all developmental stages of P. giganteum.
CONCLUSIONS
Our study provides important genomic resources for elucidating the genetic basis of advantageous traits in polyploid species, and facilitates further functional genomics research and genetic improvement of P. giganteum.
Topics: Pennisetum; Biomass; Genome, Plant; Polyploidy; Gene Expression Profiling
PubMed: 37480118
DOI: 10.1186/s12915-023-01643-w -
The New Phytologist May 2024
PubMed: 38769736
DOI: 10.1111/nph.19853 -
International Journal of Molecular... Sep 2023Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis....
Polyploidy and metastasis are associated with a low probability of disease-free survival in cancer patients. Polyploid cells are known to facilitate tumorigenesis. However, few data associate polyploidization with metastasis. Here, by generating and using diploid (2n) and tetraploid (4n) clones from malignant fibrous histiocytoma (MFH) and colon carcinoma (RKO), we demonstrate the migration and invasion advantage of tetraploid cells in vitro using several assays, including the wound healing, the OrisTM two-dimensional cell migration, single-cell migration tracking by video microscopy, the Boyden chamber, and the xCELLigence RTCA real-time cell migration. Motility advantage was observed despite tetraploid cell proliferation weakness. We could also demonstrate preferential metastatic potential in vivo for the tetraploid clone using the tail vein injection in mice and tracking metastatic tumors in the lung. Using the Mitelman Database of Chromosome Aberrations in Cancer, we found an accumulation of polyploid karyotypes in metastatic tumors compared to primary ones. This work reveals the clinical relevance of the polyploid subpopulation and the strategic need to highlight polyploidy in preclinical studies as a therapeutic target for metastasis.
Topics: Humans; Animals; Mice; Tetraploidy; Polyploidy; Chromosome Aberrations; Colonic Neoplasms
PubMed: 37762227
DOI: 10.3390/ijms241813926 -
Journal of Translational Medicine Oct 2023Polyploid giant cancer cells (PGCCs), a specific type of cancer stem cells (CSCs), can be induced by hypoxic microenvironments, chemical reagents, radiotherapy, and...
BACKGROUND
Polyploid giant cancer cells (PGCCs), a specific type of cancer stem cells (CSCs), can be induced by hypoxic microenvironments, chemical reagents, radiotherapy, and Chinese herbal medicine. Moreover, PGCCs can produce daughter cells that undergo epithelial-mesenchymal transition, which leads to cancer recurrence and disseminated metastasis. Vimentin, a mesenchymal cell marker, is highly expressed in PGCCs and their daughter cells (PDCs) and drives migratory persistence. This study explored the molecular mechanisms by which vimentin synergistically regulates PGCCs to generate daughter cells with enhanced invasive and metastatic properties.
METHODS
Arsenic trioxide (ATO) was used to induce the formation of PGCCs in Hct116 and LoVo cells. Immunocytochemical and immunohistochemical assays were performed to determine the subcellular localization of vimentin. Cell function assays were performed to compare the invasive metastatic abilities of the PDCs and control cells. The molecular mechanisms underlying vimentin expression and nuclear translocation were investigated by real-time polymerase chain reaction, western blotting, cell function assays, cell transfection, co-immunoprecipitation, and chromatin immunoprecipitation, followed by sequencing. Finally, animal xenograft experiments and clinical colorectal cancer samples were used to study vimentin expression in tumor tissues.
RESULTS
Daughter cells derived from PGCCs showed strong proliferative, migratory, and invasive abilities, in which vimentin was highly expressed and located in both the cytoplasm and nucleus. Vimentin undergoes small ubiquitin-like modification (SUMOylation) by interacting with SUMO1 and SUMO2/3, which are associated with nuclear translocation. P62 regulates nuclear translocation of vimentin by controlling SUMO1 and SUMO2/3 expression. In the nucleus, vimentin acts as a transcription factor that regulates CDC42, cathepsin B, and cathepsin D to promote PDC invasion and migration. Furthermore, animal experiments and human colorectal cancer specimens have confirmed the nuclear translocation of vimentin.
CONCLUSION
P62-dependent SUMOylation of vimentin plays an important role in PDC migration and invasion. Vimentin nuclear translocation and overexpressed P62 of cancer cells may be used to predict patient prognosis, and targeting vimentin nuclear translocation may be a promising therapeutic strategy for metastatic cancers.
Topics: Animals; Humans; Vimentin; Cell Line, Tumor; Giant Cells; Epithelial-Mesenchymal Transition; Colorectal Neoplasms; Polyploidy; Cell Movement; Tumor Microenvironment
PubMed: 37833712
DOI: 10.1186/s12967-023-04585-7 -
Autophagy Nov 2023Polyploidy is an extended phenomenon in biology. However, its physiological significance and whether it defines specific cell behaviors is not well understood. Here we...
Polyploidy is an extended phenomenon in biology. However, its physiological significance and whether it defines specific cell behaviors is not well understood. Here we study its connection to macroautophagy/autophagy, using the larval respiratory system of as a model. This system comprises cells with the same function yet with notably different ploidy status, namely diploid progenitors and their polyploid larval counterparts, the latter destined to die during metamorphosis. We identified an association between polyploidy and autophagy and found that higher endoreplication status correlates with elevated autophagy. Finally, we report that tissue histolysis in the trachea during metamorphosis is mediated by autophagy, which triggers the apoptosis of polyploid cells. APF: after pupa formation; : autophagy related; : breathless; : Cyclin E; DT: dorsal trunk; : fizzy-related; L3: larval stage 3; PBS: phosphate-buffered saline; RI: RNAi; Tr: tracheal metamere; : yorkie.
Topics: Animals; Drosophila; Trachea; Drosophila melanogaster; Drosophila Proteins; Larva; Autophagy; Polyploidy
PubMed: 37424089
DOI: 10.1080/15548627.2023.2231828 -
The Journal of General and Applied... Nov 2023Thermus thermophilus is reportedly polyploid and carries four to five identical genome copies per cell, based on molecular biological experiments. To directly detect...
Thermus thermophilus is reportedly polyploid and carries four to five identical genome copies per cell, based on molecular biological experiments. To directly detect polyploidy in this bacterium, we performed live cell imaging by X-ray free-electron laser (XFEL) diffraction and observed its internal structures. The use of femtosecond XFEL pulses enables snapshots of live, undamaged cells. For successful XFEL imaging, we developed a bacterial culture method using a starch- and casein-rich medium that produces a predominance of rod-shaped cells shorter than the focused XFEL beam size, which is slightly smaller than 2 µm. When cultured in the developed medium, the length of T. thermophilus cells, which is typically ~4 µm, was less than half its usual length. We placed living cells in a micro-liquid enclosure array and successively exposed each enclosure to a single XFEL pulse. A cell image was successfully obtained by the coherent diffractive imaging technique with iterative phase retrieval calculations. The reconstructed cell image revealed five peaks, which are most likely to be nucleoids, arranged in a row in the polyploid cell without gaps. This study demonstrates that XFELs offer a novel approach for visualizing the internal nanostructures of living, micrometer-sized, polyploid bacterial cells.
Topics: Humans; Thermus thermophilus; X-Rays; X-Ray Diffraction; Lasers; Polyploidy
PubMed: 37302826
DOI: 10.2323/jgam.2023.06.002 -
Plant Biotechnology Journal Nov 2023Peanut (Arachis) is a key oil and protein crop worldwide with large genome. The genomes of diploid and tetraploid peanuts have been sequenced, which were compared to... (Review)
Review
Peanut (Arachis) is a key oil and protein crop worldwide with large genome. The genomes of diploid and tetraploid peanuts have been sequenced, which were compared to decipher their genome structures, evolutionary, and life secrets. Genome sequencing efforts showed that different cultivars, although Bt homeologs being more privileged in gene retention and gene expression. This subgenome bias, extended to sequence variation and point mutation, might be related to the long terminal repeat (LTR) explosions after tetraploidization, especially in At subgenomes. Except that, whole-genome sequences revealed many important genes, for example, fatty acids and triacylglycerols pathway, NBS-LRR (nucleotide-binding site-leucine-rich repeats), and seed size decision genes, were enriched after recursive polyploidization. Each ancestral polyploidy, with old ones having occurred hundreds of thousand years ago, has thousands of duplicated genes in extant genomes, contributing to genetic novelty. Notably, although full genome sequences are available, the actual At subgenome ancestor has still been elusive, highlighted with new debate about peanut origin. Although being an orphan crop lagging behind other crops in genomic resources, the genome sequencing achievement has laid a solid foundation for advancing crop enhancement and system biology research of peanut.
Topics: Arachis; Genome, Plant; Domestication; Chromosome Mapping; Biological Evolution; Polyploidy
PubMed: 37523347
DOI: 10.1111/pbi.14125 -
Trends in Genetics : TIG Apr 2024Whole-genome duplications (WGDs) are widespread genomic events in eukaryotes that are hypothesized to contribute to the evolutionary success of many lineages, including... (Review)
Review
Whole-genome duplications (WGDs) are widespread genomic events in eukaryotes that are hypothesized to contribute to the evolutionary success of many lineages, including flowering plants, Saccharomyces yeast, and vertebrates. WGDs generally can be classified into autopolyploids (ploidy increase descended from one species) or allopolyploids (ploidy increase descended from multiple species). Assignment of allopolyploid progenitor species (called subgenomes in the polyploid) is important to understanding the biology and evolution of polyploids, including the asymmetric subgenome evolution following hybridization (biased fractionation). Here, I review the different methodologies used to identify the ancestors of allopolyploid subgenomes, discuss the advantages and disadvantages of these methods, and outline the implications of how these methods affect the subsequent evolutionary analysis of these genomes.
PubMed: 38637269
DOI: 10.1016/j.tig.2024.03.008