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MicroPublication Biology 2024Most mammalian cardiomyocytes become polyploid in the neonatal period, concurrent with their loss of proliferative capacity. In mice, natural or engineered mutation of...
Most mammalian cardiomyocytes become polyploid in the neonatal period, concurrent with their loss of proliferative capacity. In mice, natural or engineered mutation of the cardiomyocyte-specific kinase gene causes a higher level of diploid CMs and a higher capacity to support proliferation after adult injury. Here, we identified a polymorphism in the canine gene that is particularly common in the West Highland White Terrier breed, and show that this variant eliminates Tnni3k kinase activity. Thus, in several species, natural Tnni3k polymorphisms exist that are predicted to contribute to variation in diploid CM level and heart regenerative ability.
PubMed: 38828440
DOI: 10.17912/micropub.biology.001164 -
Computational and Structural... Dec 2024The 3D conformations of chromosomes can encode biological significance, and the implications of such structures have been increasingly appreciated recently. Certain...
The 3D conformations of chromosomes can encode biological significance, and the implications of such structures have been increasingly appreciated recently. Certain chromosome structural features, such as A/B compartmentalization, are frequently extracted from Hi-C pairwise genome contact information (physical association between different regions of the genome) and compared with linear annotations of the genome, such as histone modifications and lamina association. We investigate how additional properties of chromosome structure can be deduced using an abstract graph representation of the contact heatmap, and describe specific network properties that can have a strong connection with some of these biological annotations. We constructed chromosome structure networks (CSNs) from bulk Hi-C data and calculated a set of site-resolved (node-based) network properties. These properties are useful for characterizing certain aspects of chromosomal structure. We examined the ability of network properties to differentiate several scenarios, such as haploid vs diploid cells, partially inverted nuclei vs conventional architecture, depletion of chromosome architectural proteins, and structural changes during cell development. We also examined the connection between network properties and a series of other linear annotations, such as histone modifications and chromatin states including poised promoter and enhancer labels. We found that semi-local network properties exhibit greater capability in characterizing genome annotations compared to diffusive or ultra-local node features. For example, the local square clustering coefficient can be a strong classifier of lamina-associated domains. We demonstrated that network properties can be useful for highlighting large-scale chromosome structure differences that emerge in different biological situations.
PubMed: 38827231
DOI: 10.1016/j.csbj.2024.05.026 -
Evolutionary Bioinformatics Online 2024In diploid organisms, half of the chromosomes in each cell come from the father and half from the mother. Through previous studies, it was found that the paternal...
In diploid organisms, half of the chromosomes in each cell come from the father and half from the mother. Through previous studies, it was found that the paternal chromosome and the maternal chromosome can be regulated and expressed independently, leading to the emergence of allele specific expression (ASE). In this study, we analyzed the differential expression of alleles in the high-altitude population and the normal population based on the RNA sequencing data. Through gene cluster analysis and protein interaction network analysis, we found some changes occurred at the gene level, and some negative effects. During the study, we realized that the calmodulin homology domain may have a certain correlation with long-term survival at high altitude. The plateau environment is characterized by hypoxia, low air pressure, strong ultraviolet radiation, and low temperature. Accordingly, the genetic changes in the process of adaptation are mainly reflected in these characteristics. High altitude generation living is also highly related to cancer, immune disease, cardiovascular disease, neurological disease, endocrine disease, and other diseases. Therefore, the medical system in high altitude areas should pay more attention to these diseases.
PubMed: 38826865
DOI: 10.1177/11769343241257344 -
BMC Genomics Jun 2024Gibel carp (Carassius gibelio) is a cyprinid fish that originated in eastern Eurasia and is considered as invasive in European freshwater ecosystems. The populations of...
Reproduction-associated pathways in females of gibel carp (Carassius gibelio) shed light on the molecular mechanisms of the coexistence of asexual and sexual reproduction.
Gibel carp (Carassius gibelio) is a cyprinid fish that originated in eastern Eurasia and is considered as invasive in European freshwater ecosystems. The populations of gibel carp in Europe are mostly composed of asexually reproducing triploid females (i.e., reproducing by gynogenesis) and sexually reproducing diploid females and males. Although some cases of coexisting sexual and asexual reproductive forms are known in vertebrates, the molecular mechanisms maintaining such coexistence are still in question. Both reproduction modes are supposed to exhibit evolutionary and ecological advantages and disadvantages. To better understand the coexistence of these two reproduction strategies, we performed transcriptome profile analysis of gonad tissues (ovaries) and studied the differentially expressed reproduction-associated genes in sexual and asexual females. We used high-throughput RNA sequencing to generate transcriptomic profiles of gonadal tissues of triploid asexual females and males, diploid sexual males and females of gibel carp, as well as diploid individuals from two closely-related species, C. auratus and Cyprinus carpio. Using SNP clustering, we showed the close similarity of C. gibelio and C. auratus with a basal position of C. carpio to both Carassius species. Using transcriptome profile analyses, we showed that many genes and pathways are involved in both gynogenetic and sexual reproduction in C. gibelio; however, we also found that 1500 genes, including 100 genes involved in cell cycle control, meiosis, oogenesis, embryogenesis, fertilization, steroid hormone signaling, and biosynthesis were differently expressed in the ovaries of asexual and sexual females. We suggest that the overall downregulation of reproduction-associated pathways in asexual females, and their maintenance in sexual ones, allows the populations of C. gibelio to combine the evolutionary and ecological advantages of the two reproductive strategies. However, we showed that many sexual-reproduction-related genes are maintained and expressed in asexual females, suggesting that gynogenetic gibel carp retains the genetic toolkits for meiosis and sexual reproduction. These findings shed new light on the evolution of this asexual and sexual complex.
Topics: Animals; Female; Reproduction, Asexual; Reproduction; Carps; Male; Transcriptome; Gene Expression Profiling; Ovary; Polymorphism, Single Nucleotide
PubMed: 38824502
DOI: 10.1186/s12864-024-10462-4 -
Biotechnology For Biofuels and... May 2024The red oleaginous yeast Rhodotorula toruloides is a promising cell factory to produce microbial oils and carotenoids from lignocellulosic hydrolysates (LCH). A...
BACKGROUND
The red oleaginous yeast Rhodotorula toruloides is a promising cell factory to produce microbial oils and carotenoids from lignocellulosic hydrolysates (LCH). A multi-stress tolerant strain towards four major inhibitory compounds present in LCH and methanol, was derived in our laboratory from strain IST536 (PYCC 5615) through adaptive laboratory evolution (ALE) under methanol and high glycerol selective pressure.
RESULTS
Comparative genomic analysis suggested the reduction of the original strain ploidy from triploid to diploid, the occurrence of 21,489 mutations, and 242 genes displaying copy number variants in the evolved strain. Transcriptomic analysis identified 634 genes with altered transcript levels (465 up, 178 down) in the multi-stress tolerant strain. Genes associated with cell surface biogenesis, integrity, and remodelling and involved in stress-responsive pathways exhibit the most substantial alterations at the genome and transcriptome levels. Guided by the suggested stress responses, the multi-stress tolerance phenotype was extended to osmotic, salt, ethanol, oxidative, genotoxic, and medium-chain fatty acid-induced stresses.
CONCLUSIONS
The comprehensive analysis of this evolved strain provided the opportunity to get mechanistic insights into the acquisition of multi-stress tolerance and a list of promising genes, pathways, and regulatory networks, as targets for synthetic biology approaches applied to promising cell factories, toward more robust and superior industrial strains. This study lays the foundations for understanding the mechanisms underlying tolerance to multiple stresses in R. toruloides, underscoring the potential of ALE for enhancing the robustness of industrial yeast strains.
PubMed: 38807231
DOI: 10.1186/s13068-024-02518-0 -
The Journal of Biological Chemistry May 2024About 18% of all human cancers carry a mutation in the KRAS gene making it among the most sought-after anticancer targets. However, mutant KRas protein has proved...
About 18% of all human cancers carry a mutation in the KRAS gene making it among the most sought-after anticancer targets. However, mutant KRas protein has proved remarkably undruggable. The recent approval of the first generation of RAS inhibitors therefore marks a seminal milestone in the history of cancer research. It also raises the predictable challenges of limited drug efficacies and acquired resistance. Hence, new approaches that improve our understanding of the tumorigenic mechanisms of oncogenic RAS within more physiological settings continue to be essential. Here, we have used the near-diploid hTERT RPE-1 cells to generate isogenic cell lines in which one of the endogenous KRAS alleles carries an oncogenic KRAS mutation at glycine 12. Cells with a KRAS, KRAS, or KRAS genotype, together with WT KRAS cells, reveal that oncogenic KRAS.G12X mutations increase cell proliferation rate and cell motility and reduced focal adhesions in KRAS cells. Epidermal growth factor -induced phosphorylation of ERK and AKT was comparable between KRAS, KRAS, KRAS, and KRAS cells. Interestingly, KRAS cells showed varying responses to distinct inhibitors with the KRAS and KRAS cells more sensitive to hydroxyurea and MEK inhibitors, U0126 and trametinib, but more resistant to PI3K inhibitor, PIK-90, than the KRAS cells. A combination of low doses of hydroxyurea and U0126 showed an additive inhibition on growth rate that was greater in KRAS than WT cells. Collectively, these cell lines will be a valuable resource for studying oncogenic RAS signaling and developing effective anti-KRAS reagents with minimum cytotoxicity on WT cells.
PubMed: 38796063
DOI: 10.1016/j.jbc.2024.107409 -
Plants (Basel, Switzerland) May 2024To cultivate excellent lily germplasms, an interspecific hybrid (LC×SQ-01) was successfully obtained by using a cut-style pollination method in which the rare wild lily...
To cultivate excellent lily germplasms, an interspecific hybrid (LC×SQ-01) was successfully obtained by using a cut-style pollination method in which the rare wild lily was used as the female parent and the cut flower 'Snow Queen' was used as the male parent. The morphological features of LC×SQ-01 included height, leaf length, and width, which were observed to be between those of the parents in the tissue-cultured seedlings. The height and leaf length of LC×SQ-01 were more similar to those of the male parent, and the width was between the widths of the parents for field-generated plants. The epidermal cell length and the guard cell and stoma sizes were between those of both parents in tissue-cultured and field-generated plants. In addition, the shapes of the epidermal cells and anticlinal wall in LC×SQ-01 were more analogous to those in the male parent, while the stoma morphology was different from that of both parents. Fourteen pairs of polymorphic SSR primers were identified in both parents, and the validity of LC×SQ-01 was demonstrated by PCR amplification using five pairs of SSR primers. Flow cytometry and root tip squashing assays revealed that LC×SQ-01 was a diploid plant, similar to its parents. Furthermore, the LC×SQ-01 hybrid was more resistant to than its parents, and it also showed much greater peroxidase (POD) and catalase (CAT) activity than the parents. These results lay a foundation for breeding a new high-resistance and ornamental lily variety.
PubMed: 38794446
DOI: 10.3390/plants13101376 -
Genes Apr 2024Cellular senescence is an irreversible growth arrest that acts as a barrier to cancer initiation and progression. Histone alteration is one of the major events during...
Cellular senescence is an irreversible growth arrest that acts as a barrier to cancer initiation and progression. Histone alteration is one of the major events during replicative senescence. However, little is known about the function of H3.3 in cellular senescence. Here we found that the downregulation of H3.3 induced growth suppression with senescence-like phenotypes such as senescence-associated heterochromatin foci (SAHF) and β-galactosidase (SA-β-gal) activity. Furthermore, H3.3 depletion induced senescence-like phenotypes with the p53/p21-depedent pathway. In addition, we identified miR-22-3p, tumor suppressive miRNA, as an upstream regulator of the (H3 histone, family 3B) gene which is the histone variant H3.3 and replaces conventional H3 in active genes. Therefore, our results reveal for the first time the molecular mechanisms for cellular senescence which are regulated by H3.3 abundance. Taken together, our studies suggest that H3.3 exerts functional roles in regulating cellular senescence and is a promising target for cancer therapy.
Topics: Cellular Senescence; Humans; Histones; Tumor Suppressor Protein p53; Fibroblasts; MicroRNAs; Diploidy; Down-Regulation; Heterochromatin
PubMed: 38790171
DOI: 10.3390/genes15050543 -
BioRxiv : the Preprint Server For... May 2024Human pluripotent stem cells (hPSCs) maintain diploid populations for generations despite a persistently high rate of mitotic errors that cause aneuploidy, or chromosome...
Human pluripotent stem cells (hPSCs) maintain diploid populations for generations despite a persistently high rate of mitotic errors that cause aneuploidy, or chromosome imbalances. Consequently, to maintain genome stability, aneuploidy must inhibit hPSC proliferation, but the mechanisms are unknown. Here, we surprisingly find that homogeneous aneuploid populations of hPSCs proliferate unlike aneuploid non-transformed somatic cells. Instead, in mosaic populations, cell non-autonomous competition between neighboring diploid and aneuploid hPSCs eliminates less fit aneuploid cells. Aneuploid hPSCs with lower Myc or higher p53 levels relative to diploid neighbors are outcompeted but conversely gain a selective advantage when Myc and p53 relative abundance switches. Thus, although hPSCs frequently missegregate chromosomes and inherently tolerate aneuploidy, Myc- and p53-driven cell competition preserves their genome integrity. These findings have important implications for the use of hPSCs in regenerative medicine and for how diploid human embryos are established despite the prevalence of aneuploidy during early development.
PubMed: 38766106
DOI: 10.1101/2024.05.08.593217 -
Revista Brasileira de Ginecologia E... 2024Evaluate histological changes in testicular parameters after hormone treatment in transgender women.
OBJECTIVE
Evaluate histological changes in testicular parameters after hormone treatment in transgender women.
METHODS
Cross-section study with patients who underwent gonadectomy at Hospital de Clínicas de Porto Alegre from 2011 to 2019. Hormone treatment type, route of administration, age at initiation and duration were recorded. Atrophy parameters were observed: testicular volume, tubular diameter, basal membrane length, presence of spermatogonia and spermatids (diploid and haploid spermatozoid precursors).
RESULTS
Eighty-six patients were included. Duration of hormone treatment is associated with testicular atrophy and spermatogenesis arrest. Other characteristics of hormone treatment such as age of initiation, route of administration and type of treatment were not associated with testicular histological changes. Testicular volume may predict spermatogenesis arrest. Basal membrane length and tubular diameter ratio is an interesting predictor of germ cell presence.
CONCLUSION
Cross-sex hormone treatment affects testicular germ cell presence. Basal membrane length and tubular diameter ratio reduces inter variability of measurements and better exemplify how atrophic seminiferous tubules are. Fertility preservation should be addressed by healthcare providers in order to recognize gender affirming treatment impact on transgender health.
Topics: Humans; Male; Female; Adult; Cross-Sectional Studies; Transgender Persons; Testis; Spermatogenesis; Fertility Preservation; Young Adult; Atrophy
PubMed: 38765523
DOI: 10.61622/rbgo/2024rbgo33