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PubMed2005

Microarray analysis of immune challenged Drosophila hemocytes.

Insect hemocytes play multiple roles in immunity and carry out cellular responses like phagocytosis, encapsulation and melanization as well as producing humoral effector proteins in the first line of defense after injury and invasion of microorganisms. In this work, we used the Drosophila melanogaster hemocyte-like cell line mbn-2 and Affymetrix Drosophila GeneChips to investigate the transcriptome of a single type of immune competent tissue exposed to Gram-negative cell wall components (crude LPS) or high dose infection with live Escherichia coli. We found that gene expression profiles of both treatments overlap but show important differences in expression levels of several genes involved in immunity. In addition, cell morphology during infection was monitored and revealed distinct alterations in cell shape and adhesion. Presence of large numbers of bacteria also increased the number of cells taking on crystal cell fate. Taken together, our results indicate that hemocytes sense and respond differently to purified bacterial surface molecules and infection with live and actively growing bacteria both at the level of gene expression and in cell behavior.

Animals↗

PubMed2003

Expression profiling of the host response to bacterial infection: the transition from basal to induced defence responses in RPM1-mediated resistance.

Changes in transcription in leaves of Arabidopsis thaliana were characterised following challenge with strains of Pseudomonas syringae pv. tomato DC3000 allowing differentiation of basal resistance (hrpA mutants), gene-specific resistance (RPM1-specified interactions) and susceptibility (wild-type pathogen). In planta avirulence gene induction, changes in host [Ca2+]cyt and leaf collapse were used to delineate the transition from infection to induced resistance. The plant responds rapidly, dynamically and discriminately to infection by phytopathogenic bacteria. Within the first 2 h host transcriptional changes are common to all challenges indicating that Type III effector function does not contribute to early events in host transcriptome re-programming. The timing of induction for specific transcripts was reproducible, hierarchical and modulated at least in part through EDS1 function. R gene-specific transcripts were not observed until 3 h after inoculation. Intriguingly, the R gene-specific response proteins are expected to localise to diverse cellular addresses indicative of a global impact on cellular homeostasis. The altered transcriptional response rapidly manifests into initial symptoms of leaf collapse within 2 h, although establishment of the full macroscopic HR occurs significantly later.

Arabidopsis↗

PubMed2025

Transcriptomic profile induced by calcitriol in CaSki human cervical cancer cell line.

The vitamin D endocrine system, primarily mediated by its main metabolite calcitriol and the vitamin D receptor (VDR), plays a critical role in numerous human physiological processes, ranging from calcium metabolism to the prevention of various tumors, including cervical cancer. In this study, we comprehensively investigated the genomic regulatory effects of calcitriol in a cervical cancer model. We examined the transcriptional changes induced by calcitriol in CaSki cells, a cervical cell line harboring multiple copies of HPV16, the primary causal agent of cervical cancer. Our microarray findings, revealed that calcitriol regulated over 1000 protein-coding genes, exhibiting a predominantly repressive effect on the CaSki cell transcriptome by suppressing twice as many genes as it induced. Calcitriol decreased EPHA2 and RARA expression while inducing KLK6 and CYP4F3 expression in CaSki cells, as validated by qPCR and Western blot. Functional analysis demonstrated that calcitriol effectively inhibited key processes involved in cancer progression, including cell proliferation and migration. This was further supported by the significant downregulation of MMP7 and MMP13 mRNA levels. Our microarray results also showed that, in addition to its effects on protein-coding genes, calcitriol significantly regulates non-coding RNAs, altering the expression of approximately 400 non-coding RNAs, including 111 microRNA precursors and 29 mature microRNAs, of which 17 were upregulated and 12 downregulated. Notably, among these calcitriol-regulated microRNAs are some involved in cervical cancer biology, such as miR-6129, miR-382, miR-655, miR-211, miR-590, miR-130a, miR-301a, and miR-1252. Collectively, these findings suggest that calcitriol exhibits a significant antitumor effect in this advanced cervical cancer model by blocking critical processes for tumor progression, underscoring the importance of maintaining adequate vitamin D nutritional status.

Humans↗

PubMed2002

Gene loss, silencing and activation in a newly synthesized wheat allotetraploid.

We analyzed the events that affect gene structure and expression in the early stages of allopolyploidy in wheat. The transcriptome response was studied by analyzing 3072 transcripts in the first generation of a synthetic allotetraploid (genome S(l)S(l)A(m)A(m)), which resembles tetraploid wheat (genome BBAA), and in its two diploid progenitors Aegilops sharonensis (S(l)S(l)) and Triticum monococcum ssp. aegilopoides (A(m)A(m)). The expression of 60 out of 3072 transcripts was reproducibly altered in the allotetraploid: 48 transcripts disappeared and 12 were activated. Transcript disappearance was caused by gene silencing or by gene loss. Gene silencing affected one or both homeologous loci and was associated in part with cytosine methylation. Gene loss or methylation had occurred already in the F(1) intergeneric hybrid or in the allotetraploid, depending on the locus. The silenced/lost genes included rRNA genes and genes involved in metabolism, disease resistance, and cell cycle regulation. The activated genes with a known function were all retroelements. These findings show that wide hybridization and chromosome doubling affect gene expression via genetic and epigenetic alterations immediately upon allopolyploid formation. These events contribute to the genetic diploidization of newly formed allopolyploids.

Blotting, Northern↗

PubMed2002

Manipulation of the cell cycle by human cytomegalovirus.

The human cytomegalovirus-induced changes to the transcriptome and proteome of infected cells in many ways resemble an abortive mitogenic response. The virus induces quiescent cells to re-enter the cell cycle, but they are prevented from entering the S phase, where the synthesis of the cellular genome would compete with that of the virus for the available precursors for DNA replication. The mechanisms of these cell cycle alterations include transcriptional induction and repression, post-translational modifications and changes in protein stability. Essentially every class of cell cycle regulators is affected, and some of the key proteins are targeted by multiple different mechanisms. While the effects on cell cycle progression of viral infection, and of individual viral genes outside the context of viral infection have been described, it is now important to synthesize these two experimental approaches to gain a more complete understanding of how and why human cytomegalovirus infection affects cell cycle progression.

Animals↗

PubMed2005

Adaptation of Corynebacterium glutamicum to ammonium limitation: a global analysis using transcriptome and proteome techniques.

Theresponse of Corynebacterium glutamicum to ammonium limitation was studied by transcriptional and proteome profiling of cells grown in a chemostat. Our results show that ammonium-limited growth of C. glutamicum results in a rearrangement of the cellular transport capacity, changes in metabolic pathways for nitrogen assimilation, amino acid biosynthesis, and carbon metabolism, as well as a decreased cell division. Since transcription at different growth rates was studied, it was possible to distinguish specific responses to ammonium limitation and more general, growth rate-dependent alterations in gene expression. The latter include a number of genes encoding ribosomal proteins and genes for F(o)F(1)-ATP synthase subunits.

Adaptation, Physiological↗

PubMed2026

Nonadditive gene expression and reduced homoeolog expression bias in an intraspecific hexaploid wheat hybrid.

BACKGROUND: Intraspecific hybridization in allopolyploid plants can generate additive and nonadditive changes in gene expression through interactions between divergent parental genomes. However, how it simultaneously affects gene expression and the relative expression of homoeologs in higher-order polyploids is less well understood. To study this, we sequenced seedling leaf transcriptomes and profiled gene body methylation in two hexaploid wheat (Triticum aestivum L.) cultivars and their F₁ hybrids. RESULTS: Although only 4.3% of genes differed in expression between the parents, 22.3% deviated from mid-parent expression in the hybrids, with many showing transgressive expression. 32.1% of triads contained at least one homoeolog that deviated from mid-parent expression, and all three homoeologs deviated in 11% of triads, substantially more than expected by chance. Triads in which all three homoeologs were overexpressed also showed reduced differences in expression among homoeologs. Greater parental divergence in relative homoeolog expression was associated with nonadditive expression. Genes lacking gene body methylation were also more likely to show dominant or transgressive expression, whereas gene body methylation was associated with more balanced homoeolog expression and additive or conserved expression. CONCLUSIONS: Intraspecific hybridization in hexaploid wheat, even without a change in ploidy, was associated with widespread nonadditive gene expression and altered relative homoeolog expression within triads. These responses were associated with parental differences in homoeolog expression and the absence of gene body methylation. Although our findings are limited to seedling leaves from a single intraspecific cross, they provide a basis for testing the generality of these patterns across tissues, developmental stages, and genetic backgrounds.

Triticum↗

PubMed2026

Epigenetic and metabolic reprogramming of innate immune cells establishes immunological memory in the Schistosomiasis vector snail Biomphalaria glabrata.

Innate immune memory enables non-vertebrates to mount faster and more effective immune responses upon re-exposure to a previously encountered pathogen, yet its cellular and molecular bases remain poorly understood. The freshwater snail Biomphalaria glabrata, intermediate host of the human parasite Schistosoma mansoni, provides a powerful model to investigate this phenomenon. Here, we show that innate immune memory in B. glabrata is carried by hemocytes and relies on profound metabolic and epigenetic reprogramming initiated during primary infection. Using an integrative multi-omics approach combining transcriptomics, chromatin accessibility profiling, whole-genome bisulfite sequencing and targeted metabolomics, we reveal that the first parasite encounter induces a stable rewiring of hemocyte metabolism and chromatin landscape. This reprogramming primes hemocytes for a massive and rapid transcriptional response upon secondary challenge, characterized by an immune shift toward highly specific humoral effector pathways. Metabolic analyses demonstrate an early switch toward aerobic glycolysis, altered tricarboxylic acid cycle activity and amino acid metabolism, consistent with a Warburg-like metabolic state previously described in vertebrate trained immunity. Notably, metabolic and epigenetic remodeling occurs primarily during the primary infection and remains stable upon secondary exposure, suggesting that immune memory is encoded prior to pathogen re-encounter. Together, our results identify conserved metabolic and epigenetic mechanisms underlying innate immune memory in a non-vertebrate host and provide direct evidence that hemocyte-mediated innate immune memory in B. glabrata shares core features with trained immunity described in vertebrates.

Animals↗

PubMed2026

PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer is characterized by redox adaptation and metabolic plasticity, but the mechanisms linking these processes remain incompletely understood. Integrating bulk, single-cell, and spatial transcriptomic analyses, we identified PRDX1 as a malignant epithelial cell-associated factor linked to adverse outcome. Genetic gain- and loss-of-function studies showed that PRDX1 promoted proliferation, motility, and xenograft growth while limiting reactive oxygen species accumulation and mitochondrial apoptosis. Proteomic and biochemical analyses identified an association between PRDX1 and SCD1. PRDX1 prolonged the SCD1 protein half-life without detectably altering SCD1 transcript abundance and increased USP7-SCD1 co-precipitation. USP7 removed K48-linked polyubiquitin chains from SCD1 and prevented its proteasomal degradation, whereas catalytically inactive USP7 failed to deubiquitinate SCD1. Deletion of PRDX1 residues 157-199 weakened its association with SCD1 and reduced USP7-SCD1 co-precipitation. Depletion of SCD1 or USP7 suppressed PRDX1-dependent growth in vitro and in xenografts. These findings support a model in which PRDX1 facilitates USP7-dependent stabilization of SCD1 and promotes bladder cancer progression.

Bladder cancer↗

PubMed2026

IDH2 clonal hematopoiesis and IKAROS loss cooperate in a B-ALL subtype after lenalidomide therapy for multiple myeloma.

Lenalidomide, a maintenance treatment in multiple myeloma first-line therapy, increases the risk of secondary malignancies, including B-cell precursor acute lymphoblastic leukemia (B-ALL). We present a comprehensive molecular characterization of 57 patients with lenalidomide-associated B-ALL (LenB-ALL), revealing 3 mutational subgroups: (1) TP53mt (30%); (2) IDH2mt (p.R140Q) (23%); and (3) other, including NRAS/KRASmt. Remarkably, IDH2 R140Q mutations were highly enriched in LenB-ALL compared with those in primary B-ALL (P< .001). Furthermore, IKZF1 intragenic deletions, often subclonal and likely RAG recombinase-mediated, were observed in 54% (7/13) of IDH2mt patients with LenB-ALL. IDH2 mutations were not restricted to the leukemic clone: they persisted during measurable residual disease-negative remission and were identified in lymphoid as well as myeloid cell populations using fluorescence-activated cell sorting and single-cell RNA sequencing. This indicates a preleukemic origin of the IDH2 mutation within the context of clonal hematopoiesis. Transcriptomic and DNA methylation analyses revealed a distinct gene expression profile and a DNA hypermethylation phenotype in IDH2mt LenB-ALL, including IDH2mt-specific as well as lenalidomide-associated features. We propose that lenalidomide promotes the expansion of IDH2-mutated clonal hematopoiesis and, via IKAROS downregulation, induces a maturation arrest at the B-cell precursor stage. Subsequent genetic or epigenetic alterations render leukemogenesis independent of ongoing lenalidomide exposure. All these data define IDH2mt B-ALL as a distinct molecular subtype that is markedly overrepresented after lenalidomide treatment and highlight clonal hematopoiesis as a key contributing factor in the development of LenB-ALL.

Humans↗

PubMed2006

Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection.

Insights into the host antiviral strategies as well as viral disease manifestations can be achieved through the elucidation of host- and virus-mediated transcriptional responses. An oligo-based microarray was employed to analyse mRNAs from rhabdomyosarcoma cells infected with the MS/7423/87 strain of enterovirus 71 (EV71) at 20 h post infection. Using Acuity software and LOWESS normalization, 152 genes were found to be downregulated while 39 were upregulated by greater than twofold. Altered transcripts include those encoding components of cytoskeleton, protein translation and modification; cellular transport proteins; protein degradation mediators; cell death mediators; mitochondrial-related and metabolism proteins; cellular receptors and signal transducers. Changes in expression profiles of 15 representative genes were authenticated by real-time reverse transcription polymerase chain reaction (RT-PCR), which also compared the transcriptional responses of cells infected with EV71 strain 5865/Sin/000009 isolated from a fatal case during the Singapore outbreak in 2000. Western blot analyses of APOB, CLU, DCAMKL1 and ODC1 proteins correlated protein and transcript levels. Two-dimensional proteomic maps highlighted differences in expression of cellular proteins (CCT5, CFL1, ENO1, HSPB1, PSMA2 and STMN1) following EV71 infection. Expression of several apoptosis-associated genes was modified, coinciding with apoptosis attenuation observed in poliovirus infection. Interestingly, doublecortin and CaM kinase-like 1 (DCAMKL1) involved in brain development, was highly expressed during infection. Thus, microarray, real-time RT-PCR and proteomic analyses can elucidate the global view of the numerous and complex cellular responses that contribute towards EV71 pathogenesis.

Cell Line, Tumor↗

PubMed2025

Altered ruminal microbiome tryptophan metabolism and their derived 3-indoleacetic acid inhibit ruminal inflammation in subacute ruminal acidosis goats.

BACKGROUND: Subacute ruminal acidosis (SARA) is a digestive disorder that often severely jeopardizes the health and lactation performance of ruminants fed a high-energy diet. Different dairy ruminants exhibit varying degrees of inflammation accompanied by variations in the rumen microbiota when SARA occurs. Our understanding of the occurrence of SARA and varying degrees of rumen epithelial inflammation is lacking. Hence, we performed rumen metagenomic, metagenome-assembled genome and metabolomic analyses, with transcriptome and single-nucleus RNA sequence analyses, to explore the microbial mechanism of SARA occurrence and different degrees of inflammation. RESULTS: A total of 36 goats fed two diets with gradually increasing levels of rumen-degradable starch (RDS) were included in this study, and SARA goats fed 70% concentrate diets supplemented with whole corn (HGW-SARA) and SARA goats fed 70% concentrate diets supplemented with crushed corn (HGC-SARA) were identified. Moreover, 11 goats fed a control basal diet, named LGW-CON, were also included. Compared with those in the LGW-CON group, the rumen fermentation capacity was enhanced, accompanied by ruminal epithelial and systemic inflammation, in goats from HGW-SARA and HGC-SARA. Between them, HGC-SARA goats presented less inflammation. Notably, the ruminal inflammation-related pathways were increased only in the HGW-SARA group but not in the HGC-SARA group. Metagenomic analysis revealed that the β diversity of SARA goats was significantly different from that of LGW-CON goats. Ruminococcus significantly increased in both SARA groups, whereas Prevotella and Bacteroidales significantly decreased, which was accompanied by a decrease in cellulose and hemicellulose enzymes and an increase in lysozymes and lipopolysaccharide synthesis enzymes. Multi-omics analysis of the ruminal contents and tissues suggested that epithelial inflammation was caused by disturbed ruminal microbiome-induced Th17 cell differentiation and IL-17 signalling pathway activation. Comparative analyses between the HGW-SARA and HGC-SARA groups highlighted the importance of Selenomonas and Bifidobacterium, as well as bacterial tryptophan metabolism, in the production of 3-indoleacetic acid, which mitigated ruminal epithelial inflammation by modulating Th17 cells and inhibiting IL-17 signalling. Ruminal microbiota transplantation from HGW-SARA goats to healthy dairy goats and mice revealed the role of microbes in epithelial inflammation. Additionally, 3-indoleacetic acid supplementation reduced rumen inflammation and the IL-17 concentration in the serum, improved VFAs absorption, and enhanced milk production. CONCLUSIONS: This study unveiled that after SARA was induced by high-concentrate feeding, the rumen homeostasis was disrupted, and rumen fiber degradation capacity of dairy goats decreased, but the LPS synthesis capacity increased, and inflammation of the rumen epithelium was observed. However, the ruminal microbial species from the Bifidobacterium and Selenomonas genera and bacterial 3-indole acetic acid are pivotal in mitigating ruminal epithelial inflammation during SARA in dairy goats. This could potentially be attributed to the modulation of ruminal Th17 cell proportions and the inhibition of IL-17 signalling pathways. Video Abstract.

Rumen↗

PubMed2026

Dietary soybean or seaweed (Kappaphycus sp.) modulates taste-related gene (tas1r1 and tas1r2.2) expression in Nile tilapia (Oreochromis niloticus).

Taste perception plays a central role in fish feeding behaviour by influencing feed recognition, intake, and nutrient sensing. As aquaculture increasingly adopts plant-based ingredients to replace fishmeal, understanding how these diets affect gustatory mechanisms is critical. This study evaluated TAS-family taste receptor genes in Nile tilapia (Oreochromis niloticus) fed nutritionally formulated diets containing fishmeal (TFM), soybean meal (TSB), red seaweed (Kappaphycus sp., TSW), alongside a natural meal (TNM) reference. Fish were reared for 62 days under controlled conditions, after which growth performance was evaluated, and tongue transcriptomes were analysed using RNA sequencing to identify diet-associated gene expression changes. Candidate TAS1R and TAS2R receptors were identified through conserved domain screening and phylogenetic validation, and differential expression analysis was performed using DESeq2. Growth performance did not differ significantly among diets, although the soybean group showed the highest weight gain. Under the conditions of this study, most taste-related genes remained transcriptionally stable across formulated diets, indicating limited responsiveness of the gustatory system to ingredient substitution. Transcriptional differences were mainly observed in comparisons involving the TNM (TSB vs TNM and TSW vs TNM), where tas1r1 was upregulated, suggesting altered amino acid sensing relative to the non-formulated diet. Among formulated diets, tas1r2.2 was upregulated in the TSW vs TFM comparison, indicating potential modulation of carbohydrate-related taste pathways associated with seaweed inclusion. No reliable TAS2R transcripts were detected, likely due to low expression or tissue-specific distribution. Overall, taste receptor expression in Nile tilapia appears resilient to dietary variation, with selective modulation of TAS1R genes providing molecular insight into chemosensory adaptation to sustainable feed ingredients.

Animals↗

PubMed2026

Mapping convergent regulators of melanoma drug resistance by PerturbFate.

High-throughput genomic studies have uncovered associations between diverse genetic alterations and disease phenotypes. However, elucidating how perturbations in functionally disparate genes give rise to convergent cellular states remains challenging. Here we present PerturbFate, a high-throughput, cost-effective, combinatorial-indexing single-cell platform that enables systematic interrogation of massively parallel CRISPR interference1 perturbations across the full spectrum of gene regulation, from chromatin remodelling and nascent transcription to steady-state transcriptomic phenotypes. Using PerturbFate, we profiled more than 300,000 cultured melanoma cells to characterize multimodal phenotypic and gene regulatory responses to perturbations in more than 140 vemurafenib resistance-associated genes. We uncovered a shared dedifferentiated cell state marked by convergent cooperative transcription factor activities across diverse genetic perturbations. We further dissected phenotypic responses to perturbations in Mediator complex components, linking module-specific biochemical properties to convergent transcriptional activations. We identified common regulatory nodes that drive similar phenotypic outcomes across distinct genetic perturbations. We also delineated how perturbations in functionally unrelated genes reshape cell state. Thus, PerturbFate establishes a versatile platform for identifying key molecular regulators by anchoring multimodal regulatory dynamics to disease-relevant phenotypes.

Humans↗

PubMed2004

Towards dissecting nutrient metabolism in plants: a systems biology case study on sulphur metabolism.

A genomics analysis on sulphur metabolism has been conducted at the level of transcriptomics and metabolomics. The analysis of these data after applying bioinformatic tools is to reveal novel findings. The findings are discussed and the knowledge obtained from comparable analyses on sulphur metabolism and other plant nutrient genomic studies is reviewed. The analysis of the response of the transcriptome and metabolome to sulphur deprivation in the growth medium provides a tool set for the analysis of comparable genomics studies of other nutrients. The goal of this 'sulphobolomics' (i.e. sulphur genomics and metabolome analysis) approach, and of other investigations, is to describe in a holistic way the biochemical, molecular, and physiological response of a plant to nutrient starvation, here sulphate, or, more generally, to alterations and imbalances in nutrient availability. Eventually, this analysis will provide a case study for a systems biology approach.

Arabidopsis↗

PubMed2005

Transcriptome and selected metabolite analyses reveal multiple points of ethylene control during tomato fruit development.

Transcriptome profiling via cDNA microarray analysis identified 869 genes that are differentially expressed in developing tomato (Solanum lycopersicum) pericarp. Parallel phenotypic and targeted metabolite comparisons were employed to inform the expression analysis. Transcript accumulation in tomato fruit was observed to be extensively coordinated and often completely dependent on ethylene. Mutation of an ethylene receptor (Never-ripe [Nr]), which reduces ethylene sensitivity and inhibits ripening, alters the expression of 37% of these 869 genes. Nr also influences fruit morphology, seed number, ascorbate accumulation, carotenoid biosynthesis, ethylene evolution, and the expression of many genes during fruit maturation, indicating that ethylene governs multiple aspects of development both prior to and during fruit ripening in tomato. Of the 869 genes identified, 628 share homology (E-value < or = 1 x 10(-10)) with known gene products or known protein domains. Of these 628 loci, 72 share homology with previously described signal transduction or transcription factors, suggesting complex regulatory control. These results demonstrate multiple points of ethylene regulatory control during tomato fruit development and provide new insights into the molecular basis of ethylene-mediated ripening.

Ascorbic Acid↗

PubMed2006

Multiple microarray platforms utilized for hepatic gene expression profiling of GH transgenic coho salmon with and without ration restriction.

The objectives of this study are to examine hepatic gene expression changes caused by GH transgenesis and enhanced growth. This is the first use of cDNA microarrays to study the influence of GH transgenesis on liver gene expression in a non-mammalian vertebrate, and the first such study using sexually immature animals. Three groups of coho salmon were examined: GH transgenic on full ration (T), GH transgenic on restricted ration (R), and control non-transgenic (C). Specific growth rates for weight in T were approximately eightfold higher than in C, and fourfold higher than in R. Differential gene expression in T, R, and C samples was determined using approximately 3500 and 16,000 gene microarrays, and R and C samples were compared on a different approximately 4000 gene microarray. The use of multiple microarray platforms increased the overall proportion of the hepatic transcriptome considered in these studies. Cross-platform comparisons identified genes behaving similarly between studies. For example, genes encoding a precerebellin-like protein and complement component C3 were downregulated in R relative to C (R < C) in two microarray studies, and hemoglobins alpha and beta were R > C in all three studies. Comparisons of informative gene lists within and between studies inferred causes of altered gene expression. For example, ten genes, including 78 kDa glucose-regulated protein, glycerol-3-phosphate dehydrogenase, hemoglobins alpha and beta, and a C-type lectin, were likely induced by GH transgenesis due to their presence in both T > C and R > C gene lists. Eleven genes, including hepcidin, nuclear protein p8, precerebellin-like, transketolase, and fatty acid-binding protein, were present in both T < C and R < C gene lists and were, therefore, likely suppressed by GH transgenesis. A large number of salmonid genes identified in these studies are involved in iron homeostasis, mitochondrial function, carbohydrate metabolism, cellular proliferation, and innate immunity. Pentose phosphate pathway genes phosphogluconate dehydrogenase, transaldolase, and transketolase, were dysregulated in GH transgenic samples relative to control samples. Changes in the expression of genes involved in maintaining hemoglobin levels (heme oxygenase, hemoglobins alpha and beta, Kruppel-like globin gene activator, hepcidin) in R and T fish indicate a need for additional hemoglobin in the transgenic fish, perhaps due to higher metabolic rate required for enhanced growth.

Animals↗

PubMed2026

Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers.

UNLABELLED: Rapid-acting antidepressants like ketamine and serotonergic psychedelics show promise for treatment-resistant depression (TRD), but the molecular mechanisms that contribute to their therapeutic effects remain unclear. Induced pluripotent stem cells (iPSCs) offer a platform to model human cortical neurons and investigate drug effects in a human-relevant system. Here, iPSCs from individuals with TRD and healthy volunteers (HVs) were differentiated into mature cortical-like neurons and treated for six and 24 hours with agents being investigated as rapid-acting antidepressants, including (2R,6R)-hydroxynorketamine (HNK), psilocybin, lysergic acid diethylamide (LSD), and 2,5-Dimethoxy-4-iodoamphetamine (DOI). Bulk and single-cell RNA sequencing assessed global and cell-type-specific transcriptomic responses. Synaptic proteins were evaluated via Western blotting and immunocytochemistry. To validate translational relevance, transcriptomic results were compared to CSF proteomics from ketamine-treated HVs. Despite differing initial pharmacological targets, overall gene expression across all compounds was highly correlated at matched timepoints compared to vehicle control, suggesting shared downstream effects. Both glutamatergic and serotonergic drugs converged on pathways involving inflammation, mTORC1 signaling, and cellular growth. At the single-cell level, HNK showed distinct cell-type specific alterations: upregulation in excitatory neurons and concomitant downregulation of inhibitory neuron populations. Differentially expressed genes from HNK-treated neurons also overlapped with CSF proteomic signatures from ketamine-treated individuals, supporting the model's translational relevance. This study is the first to assess multiple putative rapid-acting antidepressants in parallel using an iPSC-derived neuron model. Both convergent and drug-specific changes in gene expression and pathway enrichment were observed across diverse compounds, supporting the use of human iPSC-derived neurons in antidepressant drug discovery. CLINICAL TRIAL REGISTRY: www.clinicaltrials.gov, NCT02484456.

Journal Article↗