Genome-wide Transcriptome Analysis Research Articles

Intralesional injection of CpG ODNs complexed with glatiramer acetate mitigates systemic cytokine toxicities and synergistically advances checkpoint blockade efficacy.

PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure. Here, we utilized glatiramer acetate (GA), the FDA-approved, lysine-rich polypeptidesto complex CpG into polycationic nanoparticles (R4B) and investigated the safety and antitumor efficacy of CpG ODNs in the murine CT26 colorectal carcinoma model. In a maximum tolerated dose study, repetitive R4B treatment displayed comparable antitumor efficacy to CpG alone treatment within a dose range from 15µg to 150µg while significantly attenuating systemic proinflammatory cytokine IL-6 release. A pharmacokinetic and biodistribution analysis confirmed that R4B localized and gradually released CpG around the lesions within 96h while 'naked' CpG quickly diffused from the injection site. Genome-wide transcriptome analysis validated that R4B treatment activated prominent TLR9-driven immune system responses in both lesions and spleens. In a CT26 multiple tumor model, intratumoral administration of R4B generated systemic immune efficacy, evidenced by an abscopal effect on untreated tumors. Notably, R4B treatment accomplished these effects with mitigated systemic proinflammatory cytokines when compared with CpG alone. We further discovered that combining R4B with anti-PD-1 treatment led to the most pronounced effects on tumor growth and longest benefits to survival time. Our investigation into possible mechanisms underlying this phenomenon included increased recruitment of cytotoxic CD8+ T cells and natural killer (NK) cells to the tumor microenvironments and the reversal of PD-L1/PD-1 axis inhibition. In summary, these results warrant further investigation for safely improving clinical responses in CPI-resistant solid tumor patients with localized CpG ODN therapy.

Host-virus interactions during infection with a wild-type ILTV strain or a glycoprotein G deletion mutant ILTV vaccine strain in an ex vivo system.

Previous studies have demonstrated the safety and efficacy of a live-attenuated glycoprotein G (gG) deletion mutant vaccine strain of ILTV (∆gG-ILTV). In the current study, transcriptional profiles of chicken tracheal organ cultures (TOCs), 24 h post inoculation with ∆gG-ILTV or the gG-expressing parent wild-type strain, CSW-1 ILTV were explored and compared with the mock-infected TOCs using RNA-seq analysis. Transcriptomes of the vaccine and wild-type ILTV were also compared with each other. Although no viral genes (except for gG) were differentially regulated between the two ILTV-infected TOCs, pair-wise comparison of the transcriptomes of the ∆gG-ILTV or the CSW-1 ILTV-infected TOCs (each compared with mock-infected TOCs) identified the similarities and differences in host gene transcription between them. Several immune checkpoint inhibitors with likely roles in ILTV-mediated immune augmentation, and gene ontologies indicating cytokine response, and cytokine signaling were upregulated in both TOCs. Additionally, several other biological processes, molecular functions, and cellular components were enriched uniquely in the ∆gG-ILTV-infected TOCs, including those that indicated modifications to tracheal extracellular matrix (ECM) structural components, which may have a role in immune modulation in vivo. This study has revealed that the modifications of transcription of host genes during the early stages of ILTV infection are not limited to changes in cytokine or chemokine gene transcription, but several other immune-related genes and ECM components. Moreover, their differential regulation in the ex vivo system appears to be influenced by gG expression, potentially affecting the outcome of ILTV infection in vivo.IMPORTANCEInfectious laryngotracheitis virus (ILTV) remains a serious threat to poultry industries worldwide, causing significant economic losses. The glycoprotein G (gG) of ILTV is a virulence factor and a chemokine-binding protein with immunoregulatory functions. The influence of gG on the transcription of select host chemokine and cytokine genes has been demonstrated previously. This study extends our understanding of the early and localized host-ILTV interactions using genome-wide transcriptome analysis of ILTV-infected chicken tracheal organ cultures, and the role of gG during the process. Differential regulation of genes encoding immune checkpoint inhibitors observed in this study may have a role in ILTV-induced inhibition of type I interferon response, or negative regulation of T cell responses, bringing clarity to these ILTV immune-evasion mechanisms. Furthermore, differential regulation of genes encoding certain structural components and receptors with roles in cell migration, in the absence of gG, is consistent with the immunomodulatory role of ILTV gG.

Physiologic and structural characterization of desisobutyryl-ciclesonide, a selective glucocorticoid receptor modulator in newborn rats.

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC). DEX but not Des-CIC caused a reduction in body weight as well as reduced insulin-like growth factor-1 serum levels and chronic hyperglycemia in neonatal rats. However, Des-CIC was as effective as DEX in reducing the expression of various bleomycin-induced proinflammatory cytokine mRNAs. In vitro studies with various cell types demonstrate the potent GR transactivation and transrepression activity of Des-CIC, although genome-wide transcriptomic analyses reveal differences in DEX vs. Des-CIC responses in neonatal rat lung and liver tissue. Des-CIC is a GR super-agonist as revealed by an in vitro coregulator peptide binding assay. In addition, molecular dynamics simulations revealed unique Des-CIC-dependent allosteric signaling pathways between specific residues in the GR ligand-binding domain and receptor surfaces interacting with coregulator peptides. Thus, Des-CIC is a potential novel selective GR modulator that could impart a favorable therapeutic index for CIC use for even modest durations of GC exposure which could have long-lasting adverse somatic, metabolic, or neurologic effects.

Transcriptome analysis reveals significant discrepancies between two in vitro models of host-trematode interaction.

Cell models emulating an in vitro parasitic infection can greatly improve our understanding of helminthiases. Nonetheless, it remains challenging to select an appropriate in vitro model to study molecular pathogenesis of infections by trematodes having a complex life cycle. Therefore, adequate models are in high demand. The epidemiologically important foodborne trematode Opisthorchis felineus parasitizes bile ducts of fish-eating mammals, including humans. The human infection leads to chronic inflammation and biliary intraepithelial neoplasia, which is considered precancerous. This study was aimed at evaluating two useful in vitro research tools based on human cholangiocytes' (H69 cells') response to the trematode: coculture with live worms or incubation with parasite-derived excretory-secretory products (ESPs). We assessed H69 cells' proliferation, migration rate, cell cycle shift, and cytokine production. We also conducted genome-wide transcriptome analysis to identify affected cascades of regulatory signaling events. We demonstrated significant discrepancies between the two in vitro models of host-parasite interactions. Although differences between the two models in cell proliferation and cell migration rate were weak, there were substantial differences in the production and release of cytokines IL-6, IL-4, and TNF. A total of 144 genes in H69 cells were found to be differentially expressed after coculture with live worms, whereas 537 genes were differentially expressed after exposure to ESPs. Transcriptomic analysis revealed only 11 common upregulated genes and six common downregulated genes. Functional enrichment analysis of the gene sets also revealed some striking differences between the in vitro models. Our data will contribute to a deeper understanding of biliary neoplasia associated with liver fluke infection. This study underscores the importance of choosing an appropriate in vitro model to accurately emulate host-parasite interactions. The data also highlight the need for further investigation into the pathogenesis of the precancerous biliary lesions associated with liver fluke infection.

Genome-wide transcriptome analysis of gene expression profiles in Goose Astrovirus-infected GEF cells

Genome-wide transcriptome analysis of gene expression profiles in Goose Astrovirus-infected GEF cells

Analysis of Plant Physiological Parameters and Gene Transcriptional Changes Under the Influence of Humic Acid and Humic Acid-Amino Acid Combinations in Maize.

The study investigated the application of humic acids (HAs) and a combination of humic acids and amino acids (HA+AA) in maize under field conditions. Based on preliminary data in the literature, the aim was to investigate the effects of the two plant conditioning compounds on plant physiological parameters. In addition to measuring plant physiological parameters in the field, a complete transcriptome analysis was performed to determine exactly which genes were expressed after the treatments and in which physiological processes they play a role. Maize plants showed significant positive yield changes after two priming treatments. Genome-wide transcriptomic analysis revealed the activation of photosynthetic and cellular respiration processes, as well as protein synthesis pathways, which explains the increased yield even under extreme precipitation conditions. The results show that the HA treatment helped in water management and increased the chlorophyll content, while the HA+AA treatment led to higher protein and dry matter contents. The post-harvest tests also show that the HA+AA treatment resulted in the highest yield parameters. Functional annotation of the maize super transcriptome revealed genes related to translation processes, photosynthesis, and cellular respiration. The combined pathway analysis showed that the HA and combined treatments activated genes related to photosynthesis, carbon fixation, and cellular respiration, providing valuable in-depth insight into the usefulness of the HA and HA+AA treatments in priming. Based on the studies, we believe that the use of natural-based humic acid plant conditioners may provide a beneficial opportunity to promote renewable, regenerative agriculture.

Genome-wide association and transcriptomic analysis and the identification of growth-related genes in Macrobrachium nipponense

Macrobrachium nipponense is a commercially important freshwater species of prawn that is widely distributed across Asian countries. In order to investigate the molecular mechanisms of growth in M. nipponense, and to provide a foundation for molecular breeding, we used genome-wide association analysis (GWAS) and transcriptomic analysis to screen polymorphisms and genes related to growth traits. We recorded the growth traits of 100 adult M. nipponense at the same growth stage, and each individual genotype was evaluated by whole genome resequencing. GWAS of growth traits detected 12 growth-related single-nucleotide polymorphisms (SNPs) and eight growth-related genes from 49 chromosomes. Of the 100 individuals, we sampled muscle tissue from a total of 18 female and male M. nipponense exhibiting large differences in growth rate for RNA-seq. Transcriptome analysis revealed a total of 27,996 unigenes; of these, 33 and 60 differentially expressed genes were identified from males and females, respectively. Of these, 12 genes associated with energy metabolism and cytoskeletal pathways were identified as growth-related genes. Notably, genes from the actin family and the ubiquitin C-terminal hydrolase 2 (UCH2) gene were identified by both GWAS and transcriptomic analysis. Two growth-related SNPs, S40_12327385 and S40_12327391, were found to be mapped to the ACTB gene. The ACTA1 gene, also from the actin family, was up-regulated in fast-growing males and females, while the ACT57B was down-regulated. In addition, the growth associated SNP S7_35313774 was located in the UCH2 gene; transcriptomics analysis revealed that the UCH2 gene was up-regulated in female individuals exhibiting high growth rates. Overall, our results provided a set of markers and candidate genes related to the growth of M. nipponense. These findings could facilitate the breeding management of this species and help us to further understand the genetic mechanisms of growth in crustaceans.

Genome-wide epigenetic profiling and transcriptome analysis in pediatric Obstructive Sleep Apnea: A focus on Black female children

Obstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder characterized by airway obstruction during sleep. Diagnosing pediatric OSA is challenging, particularly in underrepresented populations, leading to disparities in treatment and long-term negative health outcomes. Our study aimed to identify alternative diagnostic tools by investigating genome-wide epigenetic changes and associated transcriptomic alterations in Black female, pediatric patients with OSA. Whole-genome bisulfite sequencing and RNA sequencing were performed on saliva samples from healthy controls and children with OSA. Analysis of differential methylation and gene expression patterns revealed dysregulated inflammation and metabolism pathways in children with OSA. Chromosomes 19 and 22 exhibited elevated methylation signatures in this patient population. Integration of methylation and gene expression data identified specific molecular markers, including NAP1L4, CCR1, and LIF. The study emphasizes the need to consider both genetic and environmental factors in pediatric OSA, and the identified markers may offer avenues for further research.

Genome-wide association study and transcriptome analysis reveal the genetic basis underlying the environmental adaptation of plant height in a woody plant

Studies on plant height have been conducted in several crops. However, the underlying genetic mechanisms in woody plants remain unclear. To improve the genetic understanding of plant height, the genome-wide association study (GWAS) was conducted on the 298 individuals of paper mulberry (Broussonetia papyrifera), and the individuals with the highest and lowest plant heights were selected for comparative transcriptome analysis. The analysis of phenotypic data showed that plant height decreased from low latitude (N: 24°30′) to high latitude (N: 41°00′), ranging from 372 to 150 cm. Furthermore, the plant height of paper mulberry was significantly correlated with environmental factors, such as latitude, frost-free period, hours of sunshine and so on, indicating adaptive phenotypic divergence across environmental gradients. A total of 228 candidate genes were identified through the GWAS, including three genes (Bp10g0547, Bp10g0551 and Bp10g0817) that contained nonsynonymous SNP variations significantly affecting plant height. A total of 2554 differentially expressed genes (DEGs) were identified through RNA sequencing (RNA-seq) analysis, including 28, 5, 3, 20 and 138 DEGs involved in auxin, gibberellin, cytokinin, ubiquitylation and transcription factors, respectively. Besides, there were 13 common genes identified by integrating GWAS and RNA-seq analysis, including Bp10g0817, which encodes COP1 (CONSTITUTIVELY PHOTOMORPHOGENIC 1) and belongs to the RING type E3 ubiquitin ligase gene family. Collectively, this study provides valuable insights into the genetic mechanisms underlying plant height and adaptation of woody plants to diverse environments.

Overexpression of the Potato StPYL20 Gene Enhances Drought Resistance and Root Development in Transgenic Plants.

Drought is a primary limiting factor for potato growth. PYR/PYL/RCAR (referred to hereafter as PYL) proteins, as receptors for abscisic acid (ABA), play a crucial role in the plant response to drought stress. However, the underlying mechanisms of this control remain largely elusive in potatoes. In this study, a potato StPYL20 gene was identified through genome-wide investigation and transcriptome analysis under drought stress. Molecular feature analysis revealed that the StPYL20 gene exhibits the highest expression level in tubers, and is significantly up-regulated under ABA and drought stress conditions. The StPYL20 protein harbors a conserved domain exclusive to the PYL family. Further functional analysis showed that both transient and stable expressions of StPYL20 in tobacco enhanced the drought resistance of transgenic plants, resulting in increased plant height, leaf number, and fresh weight, and an improved root system. Compared to wild-type plants under drought conditions, transgenic tobacco with the StPYL20 gene exhibited lower levels of malondialdehyde (MDA), higher proline (Pro) accumulation, and increased antioxidant enzyme activity. Moreover, overexpression of the StPYL20 gene heightened the sensitivity of transgenic plants to ABA. Furthermore, StPYL20 up-regulated the expression of stress response and development-related genes in transgenic plants under drought stress. In conclusion, our findings indicated that StPYL20 enhances drought resistance and root development in transgenic plants, and plays a positive regulatory role in the potato's response to drought stress.

Characterisation of cytochrome c oxidase-coding genes from mung bean and their response to cadmium stress based on genome-wide identification and transcriptome analysis.

Cytochrome c oxidase (COX) is a crucial mitochondrial enzyme in the electron transport chain of plants, implicated in energy production and stress responses. Despite its importance, the function of COX in leguminous plants, especially under heavy metal stress like cadmium (Cd), remains understudied. In this study, COX genes (COX s) were identified based on the genome annotation file in mung bean (Vigna radiata (Linn.) R. Wilczek), and the gene structure, physicochemical properties and systematic relationships of the relevant amino acid sequences were analyzed by using bioinformatics method. The effects of Cd on the transcription levels and activities of COX in mung bean roots, stems, and leaves were detected to understand the mechanism of COX in mung bean in response to cadmium (Cd) stress. Transcriptome sequencing revealed tissue-specific expression with roots showed the highest levels. Cd stress significantly altered the expression and activity of VrCOXs, particularly in roots and stems, with varied responses among different genes. The differential response of VrCOX s to Cd stress indicates a role in the plant stress tolerance mechanism. The study provides insights into the function of COXs in legumes and a foundation for further research into Cd tolerance mechanisms, which could be vital for enhancing legume production and ensuring food safety in contaminated environments.

Transcriptional memory drives accelerated re-activation of several biosynthetic gene clusters in Aspergillus nidulans.

Organisms are repeatedly exposed to fluctuating environmental and nutritional conditions. Transcriptional memory has been shown to be a mechanism to cope with these fluctuations because it increases the speed and the magnitude of the cellular response to a certain re-occurring condition and therefore optimizes adaptation and fitness in a given environment. We found that genes coding for sterigmatocystin (ST) production in Aspergillus nidulans are activated stronger when cells are repeatedly exposed to nutrient starvation, compared to cells that experience this condition for the first time. We studied possible underlying mechanisms and found that persistence of the transcription factor AflR, which can undergo activation-inactivation cycles, accounts for a large part of the memory. In addition, a chromatin-based mechanism through histone H3 lysine 4 dimethylation (H3K4me2) and extracellular metabolites produced during the first activation phase contribute to the memory process. Genome-wide transcriptome and chromatin analyses showed that only a few genes within the ST and other starvation-induced biosynthetic gene clusters gain the H3K4me2 mark during the 1st activation, but the majority of those which receive the mark also maintain it during the subsequent repression and re-activation phase. Combined with previous findings on chromatin-level regulation of biosynthetic gene clusters (BGCs) our recent data suggest that the H3K4me2 mark may contribute to the correct 3D organization of BGCs and that this is a prerequisite for activation and transcriptional memory.

Integration of Genome-Wide Identification and Transcriptome Analysis of Class III Peroxidases in Paeonia ostii: Insight into Their Roles in Adventitious Roots, Heat Tolerance, and Petal Senescence.

As a plant-specific gene family, class III peroxidases (PODs) play an important role in plant growth, development, and stress responses. However, the POD gene family has not been systematically studied in Paeonia ostii. In this study, a total of 57 PoPOD genes were identified in the P. ostii genome. Subsequently, phylogenetic analysis and chromosome mapping revealed that PoPODs were classified into six subgroups and were unevenly distributed across five chromosomes. The gene structure and conserved motifs indicated the potential for functional divergence among the different subgroups. Meanwhile, four PoPODs were identified as tandem duplicated genes, with no evidence of segmental duplication. Using RNA-seq data from eight different tissues, multiple PoPODs exhibited enhanced expression in apical and adventitious roots (ARs). Next, RNA-seq data from AR development combined with trend analysis showed that PoPOD30/34/43/46/47/57 are implicated in the formation of ARs in tree peony. Through WGCNA based on RNA-seq, two key genes, PoPOD5/15, might be involved in heat tolerance via ABA and MeJA signaling. In addition, real-time quantitative PCR (qRT-PCR) analysis indicated that PoPOD23 may play an important role in flower senescence. These findings deepened our understanding of POD-mediated AR development, heat tolerance, and petal senescence in tree peony.

Genome-wide transcriptome analysis of Aβ deposition on PET in a Korean cohort.

Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations. RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography. DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data. Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies. Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network moduleswere associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβdeposition. Dysregulated genes were related to a NK cell-mediated immunity.

Genome wide association study and transcriptome analysis identify candidate genes regulating wheat coleoptile length.

The online version contains supplementary material available at 10.1007/s11032-024-01520-6.

Biallelic germline DDX41 variants in a patient with bone dysplasia, ichthyosis, and dysmorphic features

DDX41 (DEAD‑box helicase 41) is a member of the largest family of RNA helicases. The DEAD-box RNA helicases share a highly conserved core structure and regulate all aspects of RNA metabolism. The functional role of DDX41 in innate immunity is also highly conserved. DDX41 acts as a sensor of viral DNA and activates the STING-TBK1-IRF3-type I IFN signaling pathway. Germline heterozygous variants in DDX41 have been reported in familial myelodysplasia syndrome (MDS)/acute myeloid leukemia (AML) patients; most patients also acquired a somatic variant in the second DDX41 allele. Here, we report a patient who inherited compound heterozygous DDX41 variants and presented with bone dysplasia, ichthyosis, and dysmorphic features. Functional analyses of the patient-derived dermal fibroblasts revealed a reduced abundance of DDX41 and abrogated activation of the IFN genes through the STING-type I interferon pathway. Genome-wide transcriptome analyses in the patient’s fibroblasts revealed significant gene dysregulation and changes in the RNA splicing events. The patient’s fibroblasts also displayed upregulation of periostin mRNA expression. Using an RNA binding protein assay, we identified DDX41 as a novel regulator of periostin expression. Our results suggest that functional impairment of DDX41, along with dysregulated periostin expression, likely contributes to this patient’s multisystem disorder.

Knockdown of β-conglycinin α' and α subunits alters seed protein composition and improves salt tolerance in soybean.

Soybean is an important plant source of protein worldwide. Increasing demands for soybean can be met by improving the quality of its seed protein. In this study, GmCG-1, which encodes the β-conglycinin α' subunit, was identified via combined genome-wide association study and transcriptome analysis. We subsequently knocked down GmCG-1 and its paralogues GmCG-2 and GmCG-3 with CRISPR-Cas9 technology and generated two stable multigene knockdown mutants. As a result, the β-conglycinin content decreased, whereas the 11S/7S ratio, total protein content and sulfur-containing amino acid content significantly increased. Surprisingly, the globulin mutant exhibited salt tolerance in both the germination and seedling stages. Little is known about the relationship between seed protein composition and the salt stress response in soybean. Metabonomics and RNA-seq analysis indicated that compared with the WT, the mutant was formed through a pathway that was more similar to that of active salicylic acid biosynthesis; however, the synthesis of cytokinin exhibited greater defects, which could lead to increased expression of plant dehydrin-related salt tolerance proteins and cell membrane ion transporters. Population evolution analysis suggested that GmCG-1, GmCG-2, and GmCG-3 were selected during soybean domestication. The soybean accessions harboring GmCG-1Hap1 presented relatively high 11S/7S ratios and relatively high salt tolerance. In conclusion, knockdown of the β-conglycinin α and α' subunits can improve the nutritional quality of soybean seeds and increase the salt tolerance of soybean plants, providing a strategy for designing soybean varieties with high nutritional value and high salt tolerance.

RNA-seq Based Transcriptome Analysis Reveals Role of Myoglobin in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease which manifests as joint destruction and bone erosion, could be caused by both genetic and environmental factors. Currently, the causes of RA are unknown, and targeted therapies are often associated with side effects and contraindications. The detection rate of RA in women is higher than men (3:1), however, there is still a lack of comprehensive understanding of the relationship between sex and RA. We hypothesized gender differences in RA prevalence and their associated mechanisms by performing genome-wide transcriptome analysis of synovial biopsy samples. The results indicated that myoglobin (MB) was differentially expressed between males and females, with higher expression in males than females in healthy populations, while the opposite was observed in RA patients. MB interacted with HLA class II histocompatibility antigen, DM beta (HLA-DMB) and the inflammatory factor interleukin 6 (IL-6) in the human synovial cell line MH7A.

Elucidating the downstream pathways triggered by H2S signaling in Arabidopsis thaliana under drought stress via transcriptome analysis

ABSTRACT Hydrogen sulfide (H2S) is a crucial signaling molecule in plants. Recent studies have shown that H2S plays an equally important role as nitric oxide (NO) and hydrogen peroxide (H2O2) in plant signaling. Previous studies have demonstrated the involvement of H2S in regulating drought and other stressful environmental conditions, but the exact downstream molecular mechanisms activated by the H2S signaling molecule remain unclear. In this study, we conducted a comprehensive genome-wide transcriptomic analysis of both wild type (WT) and double mutant (lcd/des1). Arabidopsis thaliana plants were exposed to 40% polyethylene glycol (PEG) to induce drought stress and 20 µM sodium hydrosulfide (NaHS). The resulting transcriptome data were analyzed for differentially significant genes and their statistical enrichments in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results indicated significant upregulation of genes related to photosynthesis, carbon fixation, plant secondary metabolite biosynthesis, inositol and phosphatidylinositol signaling pathways, and stress-responsive pathways in mutant plants under drought stress. Mutant plants with impaired H2S signaling mechanisms displayed greater susceptibility to drought stress compared to wild-type plants. In summary, all findings highlight the pivotal role of H2S signaling in stimulating other drought-responsive signaling pathways.

Integrated Analysis Reveals Genetic Basis of Growth Curve Parameters in an F2 Designed Pig Population Based on Genome and Transcriptome Data

Appropriate growth curves can reflect more sophisticated growth patterns of animals than body weight, and thus, the identification of genes and variants related to the growth curve parameter traits contributes to revealing the fine growth and development characteristics of livestock. However, the ability of single genome-wide association analysis (GWAS) and transcriptome analyses to identify valuable genes and variants is limited. In this study, based on genome and transcriptome data, the growth curve parameter traits of hybrid pigs were analyzed, and a set of genes and variants were identified. The Gompertz–Laird growth curve model was optimized to reveal the growth pattern of F2 individuals of Duroc × Erhualian pigs over four time points. Five growth parameters were estimated, including initial body weight (W0), instantaneous growth rate per day (L), coefficient of relative growth or maturing index (k), body weight at inflection point (Wi), and average growth rate (GR). These five parameters were subjected to a genome-wide association study, differential gene expression analysis, and weighted gene co-expression network analysis (WGCNA). In the study, 336 pigs were genotyped, and 39,494 SNP markers were used for each pig in the analysis. Thirty of these pigs were also included in the transcriptomics analysis. Based on genome and transcriptome data, the integrated analyses identified five putative SNPs (including INRA0056460 on chromosome X, DRGA0004151 on chromosome 3, INRA0056460 on chromosome X, H3GA0049324 on chromosome 17, and H3GA0037747 on chromosome 13) and 15 candidate genes (PDGFA, VEGFD, CSPP1, EFHC1, PIK3C3, ZZZ3, GCC2, MAPK14, ZPR1, ISG15, ANG, CEBPD, ZHX3, CTBP2, and MYNN). The functional analysis indicated that these candidate genes played important roles in cell division and differentiation, development and aging, and skeletal muscle and fat formation. Our results provide insight into the genetic mechanisms underlying the growth and development of hybrid pigs and offer a theoretical basis for genomic breeding.