Genes最新文献

Background/objectives: Dendritic cells (DCs) are master regulators of the adaptive immune response. Inflammatory DCs (inflamDCs) can prime inflammatory T cells in, for instance, cancer and infection. In contrast, tolerogenic DCs (tolDCs) can suppress the immune system through a plethora of regulatory mechanisms in the context of autoimmunity. We successfully generated tolDCs in vitro to durably restore immune tolerance to an islet autoantigen in type 1 diabetes patients in a clinical trial. However, cancers can induce inhibitory DCs in vivo that impair anti-tumor immunity through Siglec signaling.

Methods: To connect in vivo and in vitro tolDC properties, we tested whether tolDCs generated in vitro may also employ the Siglec pathway to regulate autoimmunity by comparing the transcriptomes and protein expression of immature and mature inflamDCs and tolDCs, generated from monocytes.

Results: Both immature DC types expressed most Siglec genes. The expression of these genes declined significantly in mature inflamDCs compared to mature tolDCs. Surface expression of Siglec proteins by DCs followed the same pattern. The majority of genes involved in the different Siglec pathways were differentially expressed by mature tolDCs, as opposed to inflamDCs, and in inhibitory pathways in particular.

Conclusions: Our results show that tolDCs generated in vitro mimic tumor-resident inhibitory DCs in vivo regarding Siglec expression.

Background/Objectives: Interferon regulatory factors (IRFs) are multifunctional transcription factors that play important roles in the transcriptional regulation of interferons and in the immune response to pathogens. Therefore, studying the interferon system in fish is highly relevant in the prevention and treatment of viral diseases. Methods: In this study, five IRF genes (IRF1, IRF4, IRF5, IRF7 and IRF9) were identified and characterized in Hucho bleekeri, and their expression profiles were determined after LPS and Poly(I:C) treatment. Results: These IRFs have typical DNA-binding domains and IRF-association domains. Amino acid sequence comparison revealed high homology between these IRFs and those of other vertebrates, with the highest homology being with other salmonid fish. Phylogenetic analysis revealed that these IRFs are divided into four subfamilies (IRF1, IRF3, IRF4 and IRF5), with both IRF4 and IRF9 belonging to the IRF4 subfamily. IRF genes were widely expressed in all of the tested tissues, with IRF1, IRF4 and IRF9 being highly expressed in the spleen and kidney and IRF5 and IRF7 highly expressed in the gonads. IRF1, IRF4 and IRF5 expression was induced at different time points post-LPS challenge. IRF7 and IRF9 expression in the spleen and head kidney was not significantly altered by LPS induction. Poly(I:C) treatment altered IRF expression more significantly than LPS treatment. Poly(I:C) significantly altered the spleen and head kidney expression of all five IRFs. Conclusions: These findings reveal the potential role of IRFs in the antiviral response of H. bleekeri and provide a reference for examining signal transduction pathways in the interferon system in fish.

Background: This study explores the potential for hidden variations within seemingly uniform regions of growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs). We employed archived tissue samples using Laser Capture Microdissection Sequencing (LCM-RNAseq) to probe the molecular landscape of these tumors at a deeper level.

Methods: A customized protocol was developed to extract, process, and sequence small amounts of RNA from formalin-fixed, paraffin-embedded (FFPE) tissues derived from five patients with GH-secreting PitNETs and long-term follow-up (≥10 years). This approach ensured precise isolation of starting material of enough quality for subsequent sequencing.

Results: The LCM-RNAseq analysis revealed a surprising level of diversity within seemingly homogeneous tumor regions. Interestingly, the 30 most highly expressed genes included the well-known long noncoding RNA (lncRNA) MALAT1. We further validated the levels of MALAT1 and of other tumor-associated lncRNAs using digital droplet PCR.

Conclusions: This study demonstrates the potential of LCM-RNAseq to unlock hidden molecular diversity within archived pituitary tumor samples. By focusing on specific cell populations, we identified lncRNAs expressed at different levels within the tumors, potentially offering new insights into the complex biology of GH-secreting PitNETs. This evidence prompts further research into the role of lncRNAs in pituitary neuroendocrine tumor aggressiveness and personalized treatment strategies.

Background: The importance of embryonic stem cells (ESCs) in chickens is undeniable, as they can be applied across various fields, including animal modeling, developmental biology, cell fate research, drug screening, toxicity testing, and gene function studies. However, a widely applicable culture system for chicken ESCs has yet to be developed.

Objectives: This study aimed to investigate the effects of different culture systems on the derivation and maintenance of chicken ESCs, with a focus on optimizing the selected culture conditions.

Methods: To achieve this, we tested the effectiveness of various species-specific ESC media in the derivation and culture of chicken PGCs, while incorporating different small molecule compounds to optimize the process. The pluripotency and differentiation potential of the resulting ESC-like cells were also evaluated.

Results: The combination of PD0325901, SB431542, and LIF (R2i+LIF system) was found to be effective in generating chicken ESC-like clones. Further experiments showed that enhancing the R2i+LIF system with cytokines such as SCF and FGF2 significantly extended the culture period and increased the passage number of chicken ESC-like cells. These ESC-like cells were characterized through positive alkaline phosphatase staining and the expression of pluripotency markers POUV, NANOG, and SOX2. Additionally, differentiation assays confirmed their ability to form the three germ layers.

Conclusions: The newly developed culture system provides suitable conditions for the short-term culture of chicken ESCs. However, further optimization is required to establish a system that can sustain long-term maintenance.

First, thanks to Elgoyhen et al [...].

Background: Cotton seeds are the main byproduct of cotton crops. The phenomenon of plants failing to develop mature and full seeds is called seed embryo abortion, which leads to a decrease in seed yield and potentially causes economic losses.

Methods: We report a phenotypic evaluation of seed embryos from G. hirsutum mutant (xin w 139) and wild-type (Xin W 139) lines and a comparative RNA-seq study at four developmental stages.

Results: The field results from two years showed that the sterility rate and malformation rate of xin w 139 were significantly lower than those of Xin W 139, and the RNA-seq data revealed that the differences in the development of the seed embryos of the two lines mainly occurred after 20 days post anthesis (DPA). Differential analysis revealed a total of 29,151 differentially expressed genes (DEGs), including 2696 transcription factors (TFs), between the two lines, in which the fatty acid and glucose metabolism-related pathways were significantly enriched. These DEGs were divided into 8 clusters, with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of each cluster being annotated. Furthermore, a gene regulatory network was built using weighted correlation network analysis (WGCNA), revealing 9 key genes that play crucial roles in shaping the developmental disparities of seed embryos between the two lines, among which 3 are TFs.

Conclusions: These findings offer a foundational framework for comprehending the molecular mechanisms underlying cottonseed embryo development, as well as presenting novel genetic reservoirs for further investigations into cottonseed embryo development.

Background: The SUPV3L1 gene encodes ATP-dependent RNA helicase SUPV3L1, which is a part of the mitochondrial degradosome complex or SUV3. SUPV3L1 unwinds secondary structures of mitochondrial RNA (mtRNA) and facilitates the degradation of mtRNA molecules. A nonsense homozygous variant in the SUPV3L1 gene was recently associated with mitochondrial disease. Our study presents the second documented case of SUPV3L1 pathology in humans.

Methods: Whole-genome sequencing was performed on the NovaSeq 6000 platform using pair-end reading. Data analysis was performed with an in-house developed pipeline.

Results: The 17-year-old female patient exhibited a diverse array of symptoms, including ataxia, spastic paraparesis, cognitive deficit, optic atrophy, and horizontal gaze-evoked nystagmus. Early onset of symptoms, such as ataxic gait and nystagmus, was noted, with subsequent progression of neurological manifestations. At the time of the observation, the proband had extensive regions of hypopigmented skin patches on the body and extremities, which have progressed over time. Whole-genome sequencing revealed compound heterozygous variants in the SUPV3L1 gene: c.272-2A>G and c.1924A>C; p.(Ser642Arg). RNA analysis demonstrated splicing changes attributable to the c.272-2A>G variant. ELISA assay showed increased Complex I content in the patient's fibroblasts. This case underscores the phenotypic diversity associated with SUPV3L1 mutations, emphasizing the importance of considering mitochondrial RNA helicase dysfunction in the differential diagnosis of neurodegenerative disorders. Further elucidation of the molecular mechanisms underlying SUPV3L1-associated pathology may provide valuable insights into targeted therapeutic interventions.

Background: So far, the assembly and response mechanism of soil fungi in the ecological restoration process of lead zinc mines is still unclear.

Methods: In this study, we selected three plants for the ecological restoration of abandoned lead zinc mining areas and explored the community assembly mechanism by which soil fungi assist plants in adapting to the environment during the ecological restoration process.

Results: The results revealed that the mining of lead zinc mines led to a significant decrease in soil fungal diversity, whereas the planting of three plants significantly increased the diversity of rhizosphere fungi. Mining activities significantly reduced the abundance of soil Fusarium, Macroventuria, Cladosporium, and Solicocozyma and increased the abundance of soil Helvella. After three ecologically restored plants were planted, the abundances of Fusarium and Cladosporium increased significantly, whereas the abundance of Helvella decreased significantly. In addition, Capronia was significantly enriched in the rhizosphere soils of three plant species in the mining area. β diversity and fungal guild analysis revealed that mining activities had a great impact on fungal communities and guilds. The ecological restoration of plants changed the guilds of rhizosphere fungi, making them closer to those of the control sample. In addition, the endophyte guild was significantly enriched in the rhizosphere soil of three ecologically restored plants, increasing their adaptability.

Conclusions: The results provide a reference for screening lead zinc mine bioremediation strains and developing fungal plant joint remediation strategies.

Background: Apolipoprotein E (APOE = gene, ApoE = protein) is a glycoprotein involved in the biological process of lipid transportation and metabolism, contributing to lipid homeostasis. APOE has been extensively studied for its correlation with neurodegenerative diseases, in particular Alzheimer's disease (AD), where the possession of the epsilon 4 (E4) allele is established as a risk factor for developing AD in non-familiar sporadic forms. Recently, evidence suggests a broad involvement of E4 also in other neurological conditions, where it has been shown to be a predictive marker for worse clinical outcomes in Parkinson's disease (PD), brain trauma, and disturbances of consciousness. The mechanisms underlying these associations are complex and involve amyloid-β (Aβ) peptide accumulation and neuroinflammation, although many others have yet to be identified.

Objectives: The aim of this review is to overview the current knowledge on ApoE as a non-protagonist actor in processes underlying neurodegenerative diseases and its clinical significance in AD, PD, acquired brain trauma, and Disorders of Consciousness (DoC). Ethical implications of genetic testing for APOE variants and information disclosure will also be briefly discussed.

Introduction: Bethlem myopathy is a rare genetic disease caused by a variant mapped to 21q22, which harbors the collagen type VI alpha 2 chain (COL6A2) and collagen type VI alpha 1 chain (COL6A1) genes, and 2q37, which harbors the collagen type VI alpha 3 chain (COL6A3) gene. Disease onset can occur at any age, and the symptoms are related to those of muscular dystrophy. Since Bethlem myopathy is a rare disease, no previous studies have been conducted in Arab countries, including Saudi Arabia. Its variable presentation of nonspecific muscular contractions and severity represents a diagnostic dilemma. Case presentation: Here, we report a Saudi pediatric patient, who is 9 years old (proband), brought to the pediatric clinic of King Saud's Hospital by his mother. The boy presented with difficulty standing, walking, and running with his classmates and unaffected siblings. He has a younger sibling, aged 6 years old, who reported having a limping gait and difficulty bending his right knee. Laboratory results for the proband were unremarkable except for a slight increase in creatine kinase (CK). Whole-exome sequencing (WES) was performed for five family members, including the proband and his symptomatic brother, their mother and two asymptomatic siblings. A very rare 3' splice site acceptor intronic variant, NM_001849.4: c.1817-3C>G, located three nucleotides before exon 25, was identified in COL6A2. Bioinformatics tools (SpliceAI, dbscSNV, FATHMM-MKL, and MaxEntScan) predicted this variant as pathogenic. The proband and his 6-year-old sibling presented a homozygous genotype for the variant, whereas the mother and one asymptomatic sibling were heterozygous, and the other sibling carried homozygous wild-type alleles. Conclusions: This is the first study to report a case of Bethlem myopathy confirmed by WES in Saudi Arabia and all Arab nations. The identified variant is rare, and its segregation pattern suggests autosomal recessive inheritance. The segregation pattern and bioinformatics tool results may qualify this variant to be annotated as pathogenic, addressing the reported uncertainty of its classification. Our findings contribute to linking and filling the knowledge gap of diagnosing and managing patients with collagen VI-related myopathies, providing greater clinical and genetic understanding to the existing knowledge.