Cotton is not only the world's most important natural fiber crop, but it is also an ideal system in which to study genome evolution, polyploidization, and cell elongation. With the assembly of five different cotton genomes, a cotton-specific whole-genome duplication with an allopolyploidization process that combined the A- and D-genomes became evident. All existing A-genomes seemed to originate from the A0-genome as a common ancestor, and several transposable element bursts contributed to A-genome size expansion and speciation. The ethylene production pathway is shown to regulate fiber elongation. A tip-biased diffuse growth mode and several regulatory mechanisms, including plant hormones, transcription factors, and epigenetic modifications, are involved in fiber development. Finally, we describe the involvement of the gossypol biosynthetic pathway in the manipulation of herbivorous insects, the role of GoPGF in gland formation, and host-induced gene silencing for pest and disease control. These new genes, modules, and pathways will accelerate the genetic improvement of cotton.

Recent Advances and Future Perspectives in Cotton Research.

The Human Silencing Hub (HUSH) complex is necessary for epigenetic repression of LINE-1 elements. We show that HUSH-depletion in human cell lines and primary fibroblasts leads to induction of interferon-stimulated genes (ISGs) through JAK/STAT signaling. This effect is mainly attributed to MDA5 and RIG-I sensing of double-stranded RNAs (dsRNAs). This coincides with upregulation of primate-conserved LINE-1s, as well as increased expression of full-length hominid-specific LINE-1s that produce bidirectional RNAs, which may form dsRNA. Notably, LTRs nearby ISGs are derepressed likely rendering these genes more responsive to interferon. LINE-1 shRNAs can abrogate the HUSH-dependent response, while overexpression of an engineered LINE-1 construct activates interferon signaling. Finally, we show that the HUSH component, MPP8 is frequently downregulated in diverse cancers and that its depletion leads to DNA damage. These results suggest that LINE-1s may drive physiological or autoinflammatory responses through dsRNA sensing and gene-regulatory roles and are controlled by the HUSH complex.

/pdf/the-hush-complex-is-a-gatekeeper-of-type-i-interferon-ejmq7dqse8.pdf

The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s.

Almost all plants in the genus Populus are dioecious (i.e. trees are either male or female), but it is unknown whether dioecy evolved in a common ancestor or independently in different subgenera. Here, we sequence the small peritelomeric X- and Y-linked regions of P. deltoides chromosome XIX. Two genes are present only in the Y-linked region. One is a duplication of a non-Y-linked, female-specifically expressed response regulator, which produces siRNAs that block this gene’s expression, repressing femaleness. The other is an LTR/Gypsy transposable element family member, which generates long non-coding RNAs. Overexpression of this gene in A. thaliana promotes androecium development. We also find both genes in the sex-determining region of P. simonii, a different poplar subgenus, which suggests that they are both stable components of poplar sex-determining systems. By contrast, only the duplicated response regulator gene is present in the sex-linked regions of P. davidiana and P. tremula. Therefore, findings in our study suggest dioecy may have evolved independently in different poplar subgenera. Dioecy has evolved independently from hermaphroditic ancestors in different plant lineages. Here, the authors assemble Populus deltoides male and female genomes, and show the putative roles of a femaleness gene and a maleness gene in sex determination, which suggests independent evolution in different poplar species.

/pdf/evidences-for-a-role-of-two-y-specific-genes-in-sex-57zufrbh6s.pdf

Evidences for a role of two Y-specific genes in sex determination in Populus deltoides.

Most diploid organisms have polyploid ancestors. The evolutionary process of polyploidization is poorly understood but has frequently been conjectured to involve some form of ‘genome shock’, such as genome reorganization and subgenome expression dominance. Here we study polyploidization in Arabidopsis suecica, a post-glacial allopolyploid species formed via hybridization of Arabidopsis thaliana and Arabidopsis arenosa. We generated a chromosome-level genome assembly of A. suecica and complemented it with polymorphism and transcriptome data from all species. Despite a divergence around 6 million years ago (Ma) between the ancestral species and differences in their genome composition, we see no evidence of a genome shock: the A. suecica genome is colinear with the ancestral genomes; there is no subgenome dominance in expression; and transposon dynamics appear stable. However, we find changes suggesting gradual adaptation to polyploidy. In particular, the A. thaliana subgenome shows upregulation of meiosis-related genes, possibly to prevent aneuploidy and undesirable homeologous exchanges that are observed in synthetic A. suecica, and the A. arenosa subgenome shows upregulation of cyto-nuclear processes, possibly in response to the new cytoplasmic environment of A. suecica, with plastids maternally inherited from A. thaliana. These changes are not seen in synthetic hybrids, and thus are likely to represent subsequent evolution. Arabidopsis suecica is a natural allotetraploid species formed via hybridization of Arabidopsis thaliana and Arabidopsis arenosa. Comparative analysis of genome and transcriptome data shows no evidence for major genomic changes linked to structural and functional alterations in A. suecica but reveals changes to the meiotic machinery and cyto-nuclear processes.

/pdf/gradual-evolution-of-allopolyploidy-in-arabidopsis-suecica-1vfdm78ucy.pdf

Gradual evolution of allopolyploidy in Arabidopsis suecica.

A comprehensive overview of cotton genomics, biotechnology and molecular biological studies

Interspecific hybridization and whole genome duplication are driving forces of genomic and organism diversification. But the effect of interspecific hybridization and whole genome duplication on the non-coding portion of the genome in particular remains largely unknown. In this study, we examine the profile of long non-coding RNAs (lncRNAs), comparing them with that of coding genes in allotetraploid cotton (Gossypium hirsutum), its putative diploid ancestors (G. arboreum; G. raimondii), and an F1 hybrid (G. arboreum × G. raimondii, AD). We find that most lncRNAs (80%) that were allelic expressed in the allotetraploid genome. Moreover, the genome shock of hybridization reprograms the non-coding transcriptome in the F1 hybrid. Interestingly, the activated lncRNAs are predominantly transcribed from demethylated TE regions, especially from long interspersed nuclear elements (LINEs). The DNA methylation dynamics in the interspecies hybridization are predominantly associated with the drastic expression variation of lncRNAs. Similar trends of lncRNA bursting are also observed in the progress of polyploidization. Additionally, we find that a representative novel lncRNA XLOC_409583 activated after polyploidization from a LINE in the A subgenome of allotetraploid cotton was involved in control of cotton seedling height. Our results reveal that the processes of hybridization and polyploidization enable the neofunctionalization of lncRNA transcripts, acting as important sources of increased plasticity for plants.

/pdf/lncrnas-in-polyploid-cotton-interspecific-hybrids-are-1v0ztad0mu.pdf

LncRNAs in polyploid cotton interspecific hybrids are derived from transposon neofunctionalization.

Preeclampsia is a pregnancy-related condition that causes high blood pressure and proteinuria after 20 weeks of pregnancy. It is linked to increased maternal mortality, organ malfunction, and foetal development limitation. In this view, there is a need critical to identify biomarkers for the early detection of preeclampsia. The objective of this study is to discover critical genes and explore medications for preeclampsia treatment that may influence these genes.Four datasets, including GSE10588, GSE25906, GSE48424 and GSE60438 were retrieved from the Gene Expression Omnibus database. The GSE10588, GSE25906, and GSE48424 datasets were then removed the batch effect using the "sva" R package and merged into a complete dataset. The differentially expressed genes (DEGs) were identified using the "limma" R package. The potential small-molecule agents for the treatment of PE was further screened using the Connective Map (CMAP) drug database based on the DEGs. Further, Weight gene Co-expression network (WGNCA) analysis was performed to identified gene module associated with preeclampsia, hub genes were then identified using the logistic regression analysis. Finally, the immune cell infiltration level of genes was evaluated through the single sample gene set enrichment analysis (ssGSEA).A total of 681 DEGs (376 down-regulated and 305 up-regulated genes) were identified between normal and preeclampsia samples. Then, Dexamethasone, Prednisone, Rimexolone, Piretanide, Trazodone, Buflomedil, Scoulerin, Irinotecan, and Camptothecin drugs were screened based on these DEGs through the CMAP database. Two modules including yellow and brown modules were the most associated with disease through the WGCNA analysis. KEGG analysis revealed that the chemokine signaling pathway, Th1 and Th2 cell differentiation, B cell receptor signalling pathway and oxytocin signalling pathway were significantly enriched in these modules. Moreover, two key genes, PLEK and LEP were evaluated using the univariate and multivariate logistic regression analysis from the hub modules. These two genes were further validated in the external validation cohort GSE60438 and qRT-PCR experiment. Finally, we evaluated the relationship between immune cell and two genes.In conclusion, the present study investigated key genes associated with PE pathogenesis that may contribute to identifying potential biomarkers, therapeutic agents and developing personalized treatment for PE. 

/pdf/bioinformatics-methods-in-biomarkers-of-preeclampsia-and-20ejpcmz.pdf

Bioinformatics methods in biomarkers of preeclampsia and associated potential drug applications

Background Recent observational studies and meta-analyses have shown that vitamin C reduces cancer incidence and mortality, but the underlying mechanisms remain unclear. We conducted a comprehensive pan-cancer analysis and biological validation in clinical samples and animal tumor xenografts to understand its prognostic value and association with immune characteristics in various cancers. Methods We used the Cancer Genome Atlas gene expression data involving 5769 patients and 20 cancer types. Vitamin C index (VCI) was calculated using the expression of 11 genes known to genetically predict vitamin C levels, which were classified into high and low subgroups. The correlation between VCI and patient overall survival (OS), tumor mutational burden (TMB), microsatellite instability (MSI), and immune microenvironment was evaluated, using Kaplan-Meier analysis method and ESTIMATE (https://bioinformatics.mdanderson.org/estimate/). Clinical samples of breast cancer and normal tissues were used to validate the expression of VCI-related genes, and animal experiments were conducted to test the impact of vitamin C on colon cancer growth and immune cell infiltration. Results Significant changes in expression of VCI-predicted genes were observed in multiple cancer types, especially in breast cancer. There was a correlation of VCI with prognosis in all samples (adjusted hazard ratio [AHR] = 0.87; 95% confidence interval [CI] = 0.78–0.98; P = 0.02). The specific cancer types that exhibited significant correlation between VCI and OS included breast cancer (AHR = 0.14; 95% CI = 0.05–0.40; P < 0.01), head and neck squamous cell carcinoma (AHR = 0.20; 95% CI = 0.07–0.59; P < 0.01), kidney clear cell carcinoma (AHR = 0.66; 95% CI = 0.48–0.92; P = 0.01), and rectum adenocarcinoma (AHR = 0.01; 95% CI = 0.001–0.38; P = 0.02). Interestingly, VCI was correlated with altered immunotypes and associated with TMB and MSI negatively in colon and rectal adenocarcinoma (P < 0.001) but positively in lung squamous cell carcinoma (P < 0.05). In vivo study using mice bearing colon cancer xenografts demonstrated that vitamin C could inhibit tumor growth with significant impact on immune cell infiltration. Conclusion VCI is significantly correlated with OS and immunotypes in multiple cancers, and vitamin C might have therapeutic potential in colon cancer.

/pdf/genetically-predicted-vitamin-c-levels-significantly-affect-3bcx4ycm.pdf

Genetically predicted vitamin C levels significantly affect patient survival and immunotypes in multiple cancer types

Background A survival benefit from pulmonary resection was observed in octogenarians with non-small cell lung cancer (NSCLC). Meanwhile, the identification of patients who can indeed benefit can be difficult. Therefore, we aimed to establish a web-based predictive model to identify optimal candidates for pulmonary resection. Methods Octogenarians with NSCLC in Surveillance, Epidemiology and End Results (SEER) database were enrolled and split into the surgery and non-surgery groups based on whether they received pulmonary resection. Propensity-score matching (PSM) was utilized to eliminate the imbalance. Independent prognostic factors were identified. Patients in the surgery group who lived longer than the median cancer-specific survival (CSS) time of the non-surgery group were assumed to benefit from the surgery. The surgery group was further divided into the beneficial group and the non-beneficial group based on the median CSS time of the non-surgery group. Among the surgery group, a nomogram was established through a logistic regression model. Results A total of 14,264 eligible patients were extracted, with 4,475 (31.37%) patients receiving pulmonary resection. Surgery was an independent favorable factor of prognosis after PSM (median CSS time: 58 vs. 14 months, P<0.001). A total of 750 (70.4%) patients lived longer than 14 months (beneficial group) in the surgery group. Factors including age, gender, race, histologic type, differentiation grade, and tumor-node-metastasis (TNM) stage were used to formulate the web-based nomogram. The precise discrimination and predictive capability of the model were validated through receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions A web-based predicted model was constructed to distinguish specific patients who can indeed benefit from pulmonary resection among octogenarians with NSCLC.

/pdf/identified-optimal-candidates-for-pulmonary-resection-in-26mbduu0.pdf

Identified optimal candidates for pulmonary resection in octogenarians with non-small cell lung cancer: a web-based predictive model

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LncRNAs in polyploid cotton interspecific hybrids are derived from transposon neofunctionalization.

Bioinformatics methods in biomarkers of preeclampsia and associated potential drug applications

Genetically predicted vitamin C levels significantly affect patient survival and immunotypes in multiple cancer types

Identified optimal candidates for pulmonary resection in octogenarians with non-small cell lung cancer: a web-based predictive model