Genomics最新文献

The first dikaryotic genome of Ganoderma cultivar Zizhi S2 (56.76 Mb, 16,681 genes) has been sequenced recently. 98.15% of complete BUSCOs were recovered in this genome assembly and high-confidence annotation rate improved to 91.41%. Collinearity analysis displayed the nuclear genome were 80.2% and 93.84% similar to reference genome of G. sinense at nucleotide and amino acid levels, which presented 8,521 core genes and 880 unique orthologous gene groups. Among that, at least six functional genes (tef1-α, β-tubulin, rpb2, CaM, Mn-SOD and VeA) and a newly discovered fip gene were highly similar 99.27% ∼100% to those in reference genome. And the mt-LSU, mt-SSU and 13 PCGs in their mitogenome were also highly conserved with 99.27%–99.87% and 99.08%–100% identity, respectively. So that, this cultivar Zizhi S2 is confirmed conspecific with Ganoderma sinense (NCBI: txid1077348). The new fip gene (MN635280.1_336bp) existing a novel mutation which can be reflected on the phylogenetic tree and 3-dimensional model topology structure.

Aneuploidy generally has severe phenotypic consequences. However, the molecular basis for this has been focused on single chromosomal dosage changes. It is not clear how the karyotype of complex aneuploidies affects gene expression. Here, we identified six different double-trisomy loquat strains from Q24 progenies of triploid loquat. The differences and similarities of the transcriptional responses of different double trisomy loquat strains were studied systematically via RNA-seq. The global modulation of gene expression indicated that both cis and trans-effects coordinately regulated gene expression in aneuploid loquat to some extent, and this coordinated regulation was determined by different gene functional groups. Aneuploidy can induce specific transcriptional responses on loquat chromosomes. The differentially expressed genes exhibited regional gene expression dysregulation domains along chromosomes. Furthermore, Aneuploidy could also promote the expression of genes with moderate and high in loquats. Our results provide new insights into the genome-wide transcriptional effects of karyotypes with complex aneuploidies.

Background

Follicles are fundamental units of the ovary, regulated intricately during development. Exosomes and ovarian granulosa cells (OGCs) play pivotal roles in follicular development, yet the regulatory mechanisms governing exosomes remain elusive.

Results

High-throughput sequencing was employed to evaluate the complete transcript expression profiles of six samples (three porcine ovarian granulosa cells-exosome co-culture samples (GCE) and three porcine ovarian granulosa cells (POGCs) samples). Differential expression analysis revealed 924 lncRNAs, 35 circRNAs, 49 miRNAs, and 9823 mRNAs in the GCE group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated enrichment of differentially expressed transcripts in pathways related to cell proliferation and apoptosis. Furthermore, a ceRNA regulatory network comprising 43 lncRNAs, 6 circRNAs, 11 miRNAs, and 126 mRNAs was constructed based on intergene co-expression correlations. Seven miRNAs associated with cell proliferation and apoptosis regulation were identified within this network, encompassing 92 subnet pairs as candidate genes for further exploration of exosome regulatory mechanisms. Additionally, preliminary verification at the cellular level demonstrated that exosomal miR-200b enhances the viability of POGCs.

Conclusions

Transcriptome analysis unveiled a pivotal candidate ceRNA network potentially implicated in exosome-mediated regulation of granulosa cell proliferation and apoptosis, thereby influencing porcine follicular development. These findings offer insights into the molecular mechanisms of follicular fluid exosome regulation, encompassing both coding and non-coding RNA perspectives.

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571–158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

Alternative splicing (AS) has significant clinical relevance with cancers and is a potential source of neoepitopes. In this study, RNA-seq data of 94 solid tumor and matched adjacent normal tissues from 47 clinical patients covering nine cancer types were comprehensively analyzed using SUVA developed by ourselves. The results identified highly conserved pan-cancer differential alternative splicing (DAS) events and cancer-specific DAS events in a series of tumor samples, which in turn revealed the heterogeneity of AS post-transcriptional regulation across different cancers. The co-disturbed network between spliceosome factors (SFs) and common cancer-associated DAS was further constructed, suggesting the potential possibility of the regulation of differentially expressed SFs on DAS. Finally, the common cancer-associated DAS events were fully validated using the TCGA dataset, confirming the significant correlation between cancer-associated DAS and prognosis. Briefly, our study elucidates new insights into conservatived and specific DAS in cancer, providing valuable resources for cancer therapeutic targets.

Ischemia–reperfusion injury (IRI) is a cumulation of pathophysiological processes that involves cell and organelle damage upon blood flow constraint and subsequent restoration. However, studies on overall immune infiltration and ferroptosis in liver ischemia-reperfusion injury (LIRI) are limited. This study explored immune cell infiltration and ferroptosis in LIRI using bioinformatics and experimental validation. The GSE151648 dataset, including 40 matched pairs of pre- and post- transplant liver samples was downloaded for bioinformatic analysis. Eleven hub genes were identified by overlapping differentially expressed genes (DEGs), iron genes, and genes identified through weighted gene co-expression network analysis (WGCNA). Subsequently, the pathway enrichment, transcription factor-target, microRNA-mRNA and protein-protein interaction networks were investigated. The diagnostic model was established by logistic regression, which was validated in the GSE23649 and GSE100155 datasets and verified using cytological experiments. Moreover, several drugs targeting these genes were found in DrugBank, providing a more effective treatment for LIRI. In addition, the expression of 11 hub genes was validated using quantitative real-time polymerase chain reaction (qRT-PCR) in liver transplantation samples and animal models. The expression of the 11 hub genes increased in LIRI compared with the control. Five genes were significantly enriched in six biological process terms, six genes showed high enrichment for LIRI-related signaling pathways. There were 56 relevant transcriptional factors and two central modules in the protein-protein interaction network. Further immune infiltration analysis indicated that immune cells including neutrophils and natural killer cells were differentially accumulated in the pre- and post-transplant groups, and this was accompanied by changes in immune-related factors. Finally, 10 targeted drugs were screened. Through bioinformatics and further experimental verification, we identified hub genes related to ferroptosis that could be used as potential targets to alleviate LIRI.

Ningxiang (NX) pig has been recognized as one of the most famous Chinese indigenous breeds due to its characteristics in stress resistance. However, intestinal microbial feature and gene profiling in NX piglets have not been studied. Here, we compared the intestinal microbiome and transcriptome between NX and Duroc × Landrace × Large white (DLY) piglets and found the high enrichment of several colonic Bacteroides, Prevotella and Clostridium species in NX piglets. Further functional analyses revealed their predominant function in methane, glycolysis and gluconeogenesis metabolism. Our mRNA-sequencing data unraveled the distinct colonic gene expression between these two breeds. In particular, we showed that the improved intestinal function in NX piglets may be determined by enhanced intestinal barrier gene expression and varied immune gene expression through modulating the composition of the gut microbes. Together, our study revealed the intestinal characteristics of NX piglets, providing their potential application in improving breeding strategies and developing dietary interventions.

Increasing evidence suggests that tissue inhibitor of metalloproteinase 1 (TIMP1) played a pivotal role in immune regulation. Our study focused on examining the expression and function of TIMP1 in humans, particularly in its regulation of tumor-associated macrophages (TAMs) in papillary thyroid carcinoma (PTC). We observed an upregulation of TIMP1 in 16 different types of malignancies, including thyroid cancer. TIMP1 shaped the inflammatory TME in PTC. Inhibiting the expression of TIMP1 has been demonstrated to reduce the malignant biological traits of PTC cells. Furthermore, reducing TIMP1 expression impeded M2 macrophage polarization as well as facilitated M1 macrophage polarization in PTC. ELISA results demonstrated that downregulated TIMP1 expression correlated with decreased levels of IL10 and TGF-β in cell supernatants. Furthermore, the supernatant from polarized macrophages in the TIMP1-silenced group inhibited the motility of wild-type PTC cells. Therefore, TIMP1 may enhance the progression of PTC by stimulating the PI3K/AKT pathway via the secretion of IL10 and TGF-β, consequently influencing M2-type polarization in TAMs.

The indica rice variety Huizhan shows elite traits of disease resistance and heat tolerance. However, the underlying genetic basis of these traits is not fully understood due to limited genomic resources. Here, we used Nanopore long-read and next-generation sequencing technologies to generate a chromosome-scale genome assembly of Huizhan. Comparative genomics analysis uncovered a large chromosomal inversion and expanded gene families that are associated with plant growth, development and stress responses. Functional rice blast resistance genes, including Pi2, Pib and Ptr, and bacterial blight resistance gene Xa27, contribute to disease resistance of Huizhan. Furthermore, integrated genomics and transcriptomics analyses showed that OsHIRP1, OsbZIP60, the SOD gene family, and various transcription factors are involved in heat tolerance of Huizhan. The high-quality genome assembly and comparative genomics results presented in this study facilitate the use of Huizhan as an elite parental line in developing rice varieties adapted to disease pressure and climate challenges.

Sperm undergo a series of changes in the epididymis region before acquiring the ability to move and fertilize, and the identification of genes expressed in a region-specific manner in the epididymis provides a valuable insight into functional differences between regions. We collected epididymal tissue from three yaks and cultured epithelial cells from the caput, corpus and cauda regions of the yak epididymis using the tissue block method. RNA sequencing analysis (RNA-seq) technology was used to detect gene expression in yak epididymal caput, corpus and cauda epithelial cells. The results showed that the DEGs were highest in the caput vs. corpus comparison, and lowest in the corpus vs. cauda comparison. Six DEGs were verified by real-time fluorescence quantitative PCR (qRT-PCR), consistent with transcriptome sequencing results. The significantly enriched DNA replication pathway in the caput vs. corpus was coordinated with cell proliferation, while upregulated DEGs such as POLD1 and MCM4 were found in the DNA replication pathway. The AMPK signaling pathway was found significantly enriched in the caput vs cauda, suggesting its involvement in sperm maturation and capacitation. The TGF beta signaling pathway was screened in the corpus vs cauda and is crucial for mammalian reproductive regulation. Upregulated DEGs (TGFB3, INHBA, INHBB) are involved in the TGF beta signaling pathway. This study provides a reference for culturing yak epididymal epithelial cells in vitro, and elucidates the transcriptional profiles of epithelial cells in different segments of the epididymis, revealing the regulatory and functional differences between different segments, providing basic data for exploring the molecular mechanism of yak sperm maturation and improving the reproductive capacity of high-altitude mammals.