Genomics最新文献

Background: Ferroptosis is associated with alcoholic hepatitis (AH); however, the underlying mechanisms remain unclear.

Methods: Changes in iron content and oxidative stress in AH patients and in vivo and in vitro models were analyzed. Iron homeostasis pathways in the livers of patients with AH were investigated using RNA sequencing. AH-associated ferroptosis-related genes (FRGs) were identified using weighted gene co-expression network analysis. Hub genes were identified using machine learning methods, and their diagnostic potential for AH was assessed. The correlation between FRGs and the immune microenvironment was analyzed, and the underlying regulatory mechanism was explored. FRG expression was validated in clinical samples and in vitro and in vivo models. The role of FRGs in AH-related ferroptosis was explored through gene-silencing experiments.

Results: Significant iron deposits and oxidative stress were detected in clinical samples and in vivo and in vitro AH models. Bioinformatics identified GCLC, NQO1, and ULK1 as key FRGs linked to the immune microenvironment and AH-related pathogenic genes. A nomogram based on these FRGs accurately assessed AH risk, as validated using the calibration curve. A regulatory network involving 154 miRNAs and 136 transcription factors was mapped for FRGs. In AH patients, NQO1 was upregulated in the liver, whereas GCLC and ULK1 were downregulated. Silencing GCLC and ULK1 reduced cell viability and increased oxidative stress and ferroptosis, whereas silencing NQO1 had the opposite effect.

Conclusions: Therefore, GCLC, NQO1, and ULK1 are key AH-related FRGs, potentially serving as targets for diagnosing and treating AH.

Introduction: Resistance to lenvatinib limits the effectiveness of the targeted treatments for HCC. However, the exact mechanism behind this resistance remains elusive. Current research suggests that circular RNA (circRNA) is pivotal in mediating drug resistance during targeted treatments.

Objectives: To investigate the influence of circRNA on HCC progression and its resistance to lenvatinib.

Methods: We identified the crucial circRNA hsa_circ_0005711 (circPIK3C3) through bioinformatics. Study (in-vitro and in-vivo) on the expression of circPIK3C3 (measured by qRT-PCR) and its association with progress of HCC patients including lenvatinib resistance were performed. Techniques such as dual-luciferase reporter assays, RNA FISH, RAP, and AGO2-RIP were employed for discerning circPIK3C3's specific mechanisms related to progression of HCC and its lenvatinib resistance.

Results: Study (in-vitro and in-vivo) revealed that circPIK3C3 exhibited reduced expression and lenvatinib resistance in HCC, which was intimately tied to patient outcomes. Moreover, circPIK3C3 elevated SOX15 expression while suppressing the signaling pathway related to Wnt/β-catenin via inhibition of miR-452-5p through a competitive endogenous RNA (ceRNA) network. This, in turn, mitigated HCC progression and its resistance to lenvatinib.

Conclusion: CircPIK3C3 is instrumental in the disease progression and resistance to Lenvatinib in HCC. It presents a potential therapeutic avenue for patients with lenvatinib-resistant HCC and could serve as a valuable molecular marker for forecasting lenvatinib resistance in HCC patients.

Gleditsia sinensis Lam. (G. sinensis) as an important species within the Leguminosae family, has been utilized in Chinese medicine for centuries, and its thorns serve as a chief medicinal ingredient. The absence of a comprehensive genome database has hindered its in-depth research. In this investigation, a chromosome-level de novo genome assembly of G. sinensis 'Yulin No.1' was achieved, which harbors a 786.13 Mb sized genome with 36,408 protein-coding genes and experiences two WGD events. The comparative and evolutionary analysis unveiled the close phylogenetic relationship between G. sinensis and eight other Leguminosae species. The WGCNA and gene family analysis further indicated that GsinMYB was involved in the development of thorns. This investigation offered a high-level genome of G. sinensis, facilitating comparisons in Leguminosae species evolution and functional elucidation. It also provided key insights for further research on the molecular regulation mechanisms of thorn development in plants and the molecular breeding of G. sinensis.

Siganus guttatus and Siganus oramin are two major species that are naturally distributed along the Eastern Pacific coast and possess considerable ecological and economic value. Here, we present the construction and comparative analysis of the chromosome-level genomes of these two Siganus species. Employing a hybrid assembly strategy, we partitioned and independently assembled the PacBio, Illumina and Hi-C reads of S. guttatus and S. oramin, resulting in chromosome-level genomes. The assembly sizes (N50 size, BUSCO completeness) of the two genomes were 642.4 M (25.76 M, 98.26 %) and 502.8 M (16.98 M, 98.8 %) for S. guttatus and S. oramin, respectively, exhibiting high contiguity and integrity. This study marks the first successful assembly of chromosome-level genomes in Siganus species, along with an initial exploration of their dietary habits and habitats through comparative genomics analysis. These findings offer essential resources for comparative genomics and molecular evolution research.

Intramuscular fat is an essential component of muscle tissue, and understanding its contribution to skeletal muscle fat infiltration and meat quality, together with the underlying genetic mechanisms, is a major topic in pig husbandry. However, the composition of cell types and gene expression profiles essential for this purpose remain largely unexplored. Here, we performed single-cell transcriptome analysis on muscle tissue from adult pigs and identified 15 cell types, including three previously uncharacterized types of adipocytes: Adipocyte 1, Adipocyte 2, and Aregs. Phenotypic analysis showed their proportions correlated closely with intramuscular fat content. Based on integrated analysis of ATAC-seq with RNA-seq data, Adipocyte 1 and Aregs have gene expression profiles and transcription factor (TF) motif enrichment typical of adipocytes. On the other hand, myogenic TF motifs were enriched in marker gene promoters in Adipocyte 2, suggesting that these cells originate from muscle cells. Moreover, the marker gene promoters and lineage-specific TF expression in these three adipocyte types were conserved between pigs and humans. These findings provide deep insights towards understanding the complexity of mammalian intramuscular adipocyte types and the gene regulation underlying their organization and function.

The transition period from late pregnancy to early lactation in dairy cows involves significant metabolic changes to cope with the challenges related to energy metabolism. Muscle tissue, as the largest energy-metabolizing tissue in dairy cows, plays a crucial role in energy metabolism. Furthermore, circular RNAs (circRNAs) have been shown to play key roles in various biological events. However, the regulatory mechanisms of energy metabolism and muscle cells mediated by circRNAs in the muscle tissue of ketotic dairy cows remain unclear. Here, we identified a total of 5103 circRNAs in the muscle tissue of ketosis-affected cows. Among these, compared to healthy cows, 57 circRNAs were differentially expressed in the muscle tissue of ketosis-affected cows, with 39 upregulated and 18 downregulated. Functional enrichment analysis based on the source genes of circRNAs indicated that circ-30,628 is closely related to carbon metabolism, and circ-CoQ₂ is associated with mitochondrial energy metabolism. Given the sponge effect of circRNAs on miRNAs, we further predicted the network relationships of downstream miRNAs and mRNAs of circ-30,628 and circ-CoQ₂, and found that their downstream target genes are involved in signaling pathways such as MAPK, Wnt, FoxO, and autophagy, which is associated with the proliferation, differentiation, energy metabolism, oxidative stress, and mitochondrial function of muscle cells. In summary, these findings provide a theoretical basis for understanding the functions of circRNAs regulating energy metabolism in the muscle tissue of ketosis-affected cows, thereby reducing the accumulation of ketone bodies to prevent the occurrence of ketosis in dairy cows.

N6-methyladenosine (m6A) modification of RNA is a critical post-transcriptional modification, that dynamically contributes to testicular development and spermatogenesis. Nevertheless, the investigation into the role of m6A in testicular development of sheep remains insufficient. Herein, we conducted a comprehensive analysis of the m6A transcriptome landscape in the testes of F1 hybrid Southdown × Hu sheep across M0 (0 months old, newborn), M3 (3 months old, sexually immature), M6 (6 months old, sexually mature), and Y1 (1 years old, adult). By profiling the m6A signatures across the transcriptome, we observed distinct differences in m6A modification patterns during sheep testicular development. Our cross-analysis of m6A and mRNA expression revealed that the expression of 743 genes and their m6A modification were concurrent. Notably, the combined analysis of the two comparative groups, M0 vs. M6 and M0 vs. Y1, exhibited a positive correlation, with 30 candidate genes each located within the largest protein-protein interaction network. Intriguingly, eight key hub genes (VEGFA, HDAC9, ZBTB40, KDM5B, MTRR, EAPS1, TSSK3, and BMP4) were identified to be associated with the regulation of sheep testicular development and spermatogenesis. These findings contribute to a deeper understanding of the dynamic role of m6A modification in sheep testicular biology. This study to map RNA m6A modification in sheep testes at different ages, providing novel insights into m6A topology and the molecular mechanisms associated with spermatogenesis in Southdown × Hu sheep F1 hybrids and laying the foundation for further investigations of mammalian spermatogenesis.

Dendrobium is divided into ornamental and medicinal varieties due to ornamental and medicinal values. However, current research mainly focuses on medicinal Dendrobium, with less study on the medicinal value of ornamental Dendrobium. We analyzed the microstructures, active components of the stems from twelve ornamental Dendrobium, and explored the biosynthetic networks of these active components based on transcriptome sequencing. This study found the Dendrobium with the highest content of polysaccharide, alkaloid, and flavonoid was Dendrobium aphyllum (53.89 %), Dendrobium thyrsiflorum (2.11 %) and Dendrobium loddigesii (7.21 %). Further research revealed 9 DEGs associated with polysaccharide biosynthesis were highly expressed in D. aphyllum; 4 DEGs related to alkaloid biosynthesis were highly expressed in D. thyrsiflorum; 8 DEGs associated with flavonoid biosynthesis were highly expressed in D. loddigesii. This study revealed the potential medicinal value of ornamental Dendrobium and the synthetic mechanisms of its medicinal components, providing a foundation for the medical applications of ornamental Dendrobium.

Sinojackia sarcocarpa, an endangered ornamental plant endemic to China, faces germination challenges that contribute to its endangered status. The mechanisms of its seed dormancy are not well understood. This study used morphological, physiological, transcriptomic, and gene function analyses to investigate these mechanisms. Our research shows that seed dormancy in Sinojackia sarcocarpa involves both physical and physiological factors. We found that removing the hard endocarp and applying gibberellic acid can effectively break dormancy. Transcriptomic analysis identified 2218 up-regulated and 374 down-regulated genes during germination. Notably, DOG1-domain genes SsDOGL4, SsTGA9, and SsTGA10 were significantly downregulated, while SsDOG1 was not. Additionally, overexpression of SsDOGL4 in Arabidopsis endosperm was found to enhance seed dormancy. Collectively, these findings offer significant insights into the mechanisms underlying seed dormancy in this endangered plant species.

Background: Current endometrial receptivity analysis is invasive, preventing embryo transfer during the biopsy cycle. This study aims to screen serum sncRNAs as non-invasive biomarkers for ERA tests.

Methods: The study included 12 infertile patients undergoing IVF-ET and ERA, whose serum samples were collected for high-energy sequencing technology to detect sncRNA expression profiles. We overexpressed and knocked down tsRNA-35:73-Asp-GTC-1 in the decidualized Immortalized Human Eutopic Endometrial Stromal Cells (HESC) model cultured in vitro to further investigate the its effect on decidualization. The predicted tsRNA-35:73-Asp-GTC-1 target gene was verified by PCR analysis.

Results: We screened 286 differentially expressed tsRNAs, 46 miRNAs, and 106 piRNAs. KEGG analysis indicated that differentially expressed tsRNAs were associated with pathways such as 'Calcium signaling pathway,' 'Sphingolipid signaling pathway,' etc. The results of RT-qPCR validation showed that the trends of four significantly differentially expressed tsRNAs in serum and endometrium were consistent with sequencing results. ROC curves demonstrated that these four tsRNAs have good predictive value for endometrial receptivity. Overexpression of tsRNA-35:73-Asp-GTC-1 affected the morphology of decidualized cells, and the decidualization indicators also showed a decreasing trend. While knocking down tsRNA-35:73-Asp-GTC-1 had the opposite effect. The RT-qPCR results showed that tsRNA-35:73-Asp-GTC-1 was associated with the Wnt3 target gene.

Conclusion: Serum sncRNA analysis shows potential for studying the molecular mechanisms of endometrial receptivity. Four serum tsRNAs can serve as novel biomarkers for non-invasive endometrial receptivity detection. TsRNA-35:73-Asp-GTC-1 may further regulate endometrial receptivity by targeting Wnt3.