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Results for “Transcriptomic alterations”

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PubMed2026

Diving Deeper Into Mechanisms of Acrylamide-Induced Toxicity: RNA Sequencing Reveals Transcriptomic Alteration and Retrotransposon Expression in Drosophila melanogaster.

Given the inevitability of human and animal exposure to acrylamide, there is increasing concern regarding its potential health risks. While a number of molecular mechanisms have been proposed, the complexity of acrylamide toxicological pathways and interactions remains incompletely characterized. In this study, we employed a transcriptomic approach to investigate the transcriptional responses of Drosophila melanogaster following exposure to acrylamide (100 mg/kg). Our analysis identified 634 differentially expressed genes (DEGs), with 362 upregulated and 272 downregulated. Functional analysis revealed these DEGs are enriched in pathways related to reproduction, detoxification, cellular and metabolic processes, signaling, synaptic formation and organization. Notably, acrylamide exposure upregulated the expression of tau and beta-amyloid protein precursor-like genes, both implicated in Alzheimer's disease pathology. An aversive memory test further demonstrated that acrylamide impaired the short-term memory of treated flies. Additionally, acrylamide-induced toxicity altered the expression of nine long terminal repeat retrotransposons, belonging to the gypsy and pao superfamilies. By exploring the potential role of transposable element activity in acrylamide-mediated toxicity, this study provides novel insights into the molecular mechanisms underlying its effects. Collectively, these findings offer a more comprehensive understanding of the mechanisms and pathways associated with the toxic action and detoxification of acrylamide in D. melanogaster.

Animals↗

PubMed2026

Primary Tumor Epigenetic and Transcriptomic Alterations Associated with Nodal Burden and Metastatic Risk in ER+/HER2- Breast Cancer.

De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2- disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2- tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23-0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48-1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination.

Humans↗

PubMed2024

Transcriptomic analysis reveals key molecular signatures across recovery phases of hemorrhagic fever with renal syndrome.

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during the recovery phases of HFRS. METHODS: RNA sequencing was employed to analyze the transcriptomic alterations in peripheral blood mononuclear cells from HFRS patients across the oliguric phase (OP), diuretic phase (DP), and convalescent phase (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR in larger sample sets. RESULTS: Our analysis revealed pronounced transcriptomic differences between DP and OP, with 38 DEGs showing consistent expression changes across all three phases. Notably, immune checkpoint genes like CD83 and NR4A1 demonstrated a monotonic increase, in contrast to a monotonic decrease observed in antiviral and immunomodulatory genes, including IFI27 and RNASE2. Furthermore, this research elucidates a sustained attenuation of immune responses across three phases, alongside an upregulation of pathways related to tissue repair and regeneration. CONCLUSION: Our research reveals the transcriptomic shifts during the recovery phases of HFRS, illuminating key genes and pathways that may serve as biomarkers for disease progression and recovery.

Hemorrhagic Fever with Renal Syndrome↗

PubMed2026

DREAMS illuminates spatial DNA and RNA modification landscapes.

DNA and RNA modifications regulate gene expression and RNA processing, but their spatial organization in complex tissues remains elusive. Here we developed DNA RNA Elements Areal Mass Spectrometry (DREAMS), a mass spectrometry imaging platform that spatially maps diverse nucleic acid modifications simultaneously. Applying DREAMS to TET-deficient mouse brains (Tet1Δ/Δ and triple Tet1/2/3Δ/Δ), we uncover TET1's unexpected role in modulating N1-methyladenosine (m1A), a pivotal RNA modification. While DREAMS reveals broad modification landscapes altered across TET knockouts, we identify TET1-mediated changes in m1A that correlate with transcriptome alterations. Our work establishes DREAMS as a transformative tool for spatial epigenomics/epitranscriptomics and suggests that TET enzymes could influence multiple DNA and RNA modifications with potential gatekeeping roles in nucleic acid regulation.

Animals↗

PubMed2024

Molecular analysis of primary and metastatic sites in patients with renal cell carcinoma.

BACKGROUNDMetastases are the hallmark of lethal cancer, though underlying mechanisms that drive metastatic spread to specific organs remain poorly understood. Renal cell carcinoma (RCC) is known to have distinct sites of metastases, with lung, bone, liver, and lymph nodes being more common than brain, gastrointestinal tract, and endocrine glands. Previous studies have shown varying clinical behavior and prognosis associated with the site of metastatic spread; however, little is known about the molecular underpinnings that contribute to the differential outcomes observed by the site of metastasis.METHODSWe analyzed primary renal tumors and tumors derived from metastatic sites to comprehensively characterize genomic and transcriptomic features of tumor cells as well as to evaluate the tumor microenvironment at both sites.RESULTSWe included a total of 657 tumor samples (340 from the primary site [kidney] and 317 from various sites of metastasis). We show distinct genomic alterations, transcriptomic signatures, and immune and stromal tumor microenvironments across metastatic sites in a large cohort of patients with RCC.CONCLUSIONWe demonstrate significant heterogeneity among primary tumors and metastatic sites and elucidate the complex interplay between tumor cells and the extrinsic tumor microenvironment that is vital for developing effective anticancer therapies.

Humans↗

PubMed2026

Identification of cryosensitive niches and a targetable FOS/AP‑1 program in the human ovarian cortex by single‑cell and spatial transcriptomics.

BACKGROUND: The ovary is a vital and dynamic reproductive organ. Ovarian tissue cryopreservation (OTC) plays a vital role in preserving female fertility. However, the cellular subtypes most susceptible to cryoinjury and the molecular mechanisms underlying cryopreservation-associated damage remain poorly understood. This study aimed to identify cell populations vulnerable to freezing-thawing and to elucidate the key transcriptomic alterations and signaling pathways associated with ovarian cryoinjury at the single-cell and spatial levels. METHODS: Ovarian cortical tissues from patients undergoing three gender reassignment surgery (GRS) were divided into fresh and vitrification-rapid warming groups. Following collagenase IV digestion, 10x Genomics single-cell RNA-seq was used for dissociated ovarian cell suspensions (27,185 fresh and 25,480 frozen-thawed cells). Eight major cell clusters were identified. Additionally, 110 oocytes (66 fresh, 44 vitrification-rapid warming) were isolated and analyzed using the Smart-seq2 platform. Spatial transcriptomics was performed via BGI Stereo-seq. Molecular validation was performed via β-galactosidase staining, immunofluorescence, and qRT-PCR. RESULTS: Cryopreservation significantly altered the activity of pathways related to focal adhesion, oxidative stress, and apoptosis, particularly in stromal and perivascular cells. The number of FOS-positive perivascular cells was notably increased after vitrification-rapid warming, whereas the number of PTGDS-positive stromal cells decreased. Oocyte analysis revealed that cryopreservation primarily disrupted pathways involved in the cell cycle and meiosis, although the damage was not irreversible, supporting the relative safety of long-term cryostorage. Spatial transcriptomics and functional validation further confirmed the rapid and robust activation of the FOS/AP-1 pathway after vitrification-rapid warming, particularly in perivascular and granulosa cells. Treatment with T-5224 (a FOS/AP-1 inhibitor) significantly rescued the morphology and function of cultured frozen-thawed ovaries. CONCLUSIONS: Stromal and perivascular cells are the main cell types that are sensitive to ovarian cryopreservation. The FOS/AP-1 pathway is markedly activated after, suggesting the exacerbation of metabolic impairment. In oocytes within the ovarian cortex, the cell cycle and meiosis-related physiological processes were the primary processes affected.

Female↗

PubMed2026

Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.

Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4+ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.

TCR/BCR↗

PubMed2026

Genomic and transcriptomic features of relapsed small cell lung cancer.

BACKGROUND: Relapsed small cell lung cancer is characterized by treatment resistance and poor outcomes. Genomic and transcriptomic alterations in relapsed SCLC have not been characterized well. We comprehensively profiled relapsed SCLC samples along with patient-matched treatment-naive samples, when available, using whole-exome (WES), whole-genome (WGS), and RNA-sequencing (RNA-seq) to describe the molecular landscape of relapsed SCLC. Our goal is to identify potential novel pathways for additional functional validation and eventually novel therapeutic options. METHODS: We analyzed 54 relapsed and 27 treatment-naive SCLC samples using WES (with 26 patient-matched paired samples). A subset of the samples was also analyzed by WGS (n=28) and RNA-seq (n=31). Differences in mutational signatures, gene expression, structural variants, splicing, and neoantigen profiles at diagnosis and relapse were investigated. RESULTS: Relapsed SCLC samples demonstrated mutation signatures characteristic of platinum and APOBEC mutagenesis. Furthermore, these samples were characterized by MYC, MYCL and MYCN amplifications. Both treatment-naive and relapsed SCLC samples showed high prevalence of mutation-associated neoantigens (median= 86 in treatment-naive and 90 in relapsed SCLC; p=0.8) and TP53 was the most frequently altered gene to result in a neoantigen (48% of analyzed samples). Potential mechanisms of immune evasion, including amplification of CD24, overexpression of IDO1, increased M2 macrophage presence, and upregulation of HLA-E were also observed in relapse samples. Differences in alternative splicing patterns were observed between treatment-naive and relapsed small cell samples. Retained intron events were significantly enriched in treatment-naive samples and affected genes involved in DNA repair, metabolism, and WNT and MYC pathways. CONCLUSIONS: This study highlights the genomic and transcriptomic features of relapsed SCLC. These samples were characterized by genomic instability, WNT and MYC dysregulation, and splicing aberrations. Additional studies targeting the splicing machinery, WNT signaling, and immune evasion pathways could identify novel therapeutic vulnerabilities in SCLC.

Journal Article↗

PubMed2024

Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B.

Testicular germ cell tumors (TGCTs) can be treated with cisplatin-based therapy. However, a clinically significant number of cisplatin-resistant patients die from progressive disease as no effective alternatives exist. Curative cisplatin therapy results in acute and life-long toxicities in the young TGCT patient population providing a rationale to decrease cisplatin exposure. In contrast to genetic alterations, recent evidence suggests that epigenetics is a major driving factor for TGCT formation, progression, and response to chemotherapy. Hence, targeting epigenetic pathways with "epidrugs" is one potential relatively unexplored strategy to advance TGCT treatment beyond cisplatin. In this report, we demonstrate for the first time that targeting polycomb demethylases KDM6A and KDM6B with epidrug GSK-J4 can treat both cisplatin-sensitive and -resistant TGCTs. While GSK-J4 had minimal effects alone on TGCT tumor growth in vivo, it dramatically sensitized cisplatin-sensitive and -resistant TGCTs to cisplatin. We validated KDM6A/KDM6B as the target of GSK-J4 since KDM6A/KDM6B genetic depletion had a similar effect to GSK-J4 on cisplatin-mediated anti-tumor activity and transcriptome alterations. Pharmacologic and genetic targeting of KDM6A/KDM6B potentiated or primed the p53-dominant transcriptional response to cisplatin, with also evidence for basal activation of p53. Further, several chromatin modifier genes, including BRD4, lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development.

Testicular Neoplasms↗

PubMed2026

Comprehensive Profiling of Claudin 18.2 Immunohistochemical Expression in 564 Surgically Resected Gastric and Gastroesophageal Junction Adenocarcinomas.

Claudin 18 isoform 2 (CLDN18.2) is a novel therapeutic target for advanced, HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma positive for CLDN18.2 immunohistochemical (IHC) expression, defined as ≥75% tumor cells with moderate-to-strong membranous staining. Clinical studies for emerging CLDN18.2-targeted therapeutics have used less stringent enrollment criteria to test the efficacy of such therapies in patients with moderate-to-low CLDN18.2 IHC expression. Anticipating the advent of such treatments, this study aimed to provide a comprehensive survey of CLDN18.2 expression using a clinical trial-validated CLDN18.2 monoclonal antibody in surgically resected gastric/GEJ adenocarcinomas and characterize CLDN18.2-positive carcinomas using both high- and low-expression thresholds. Crisp membranous CLDN18.2 staining was detected in 59% (335/564) carcinomas, including 57% (164/286) of gastric and 62% (171/278) of GEJ adenocarcinomas. Most gastric (147/164, 90%) and GEJ (166/171, 97%) adenocarcinomas with staining demonstrated moderate or strong staining intensity. Using the high-expression threshold (≥75% tumor cells with moderate-to-strong staining), positive CLDN18.2 expression was observed in 20% (57/286) of gastric and 27% (75/278) of GEJ adenocarcinomas and was associated with Epstein-Barr virus status (P < .001) and stage I gastric adenocarcinomas (P = .02) but stage IV GEJ adenocarcinomas (P = .03). Using a low-expression threshold (≥10% tumor cells with membranous staining), positive CLDN18.2 remained significantly associated with stage I (P = .004) and showed an unadjusted association with improved disease-specific survival in gastric adenocarcinomas (P = .045), which was not retained in multivariable analysis. Whole transcriptomic analysis showed concordance between IHC and CLDN18 messenger RNA expression. Transcriptomic alterations in CLDN18.2 IHC-positive gastric adenocarcinomas included pathways in drug resistance and tumor invasion. In summary, our study presents a detailed characterization of the prevalence and distribution of CLDN18.2 IHC expression patterns. Our results showed that 59% surgically resected gastric/GEJ adenocarcinomas exhibited CLDN18.2 staining. CLDN18.2 IHC positivity defined by both high- and low-expression thresholds may be associated with early-stage gastric adenocarcinoma. These findings expand our recognition of patients who may benefit from CLDN18.2-targeted therapy.

CLDN18.2↗

PubMed2025

Deciphering the Impact of Temperature on Pleiotropic Consequences of RNA Polymerase Mutations.

Despite occurring in an essential molecule, mutations in RNA polymerase readily emerge and elicit complex pleiotropic effects across different levels of biological organization, which are all modulated by environment. We investigated the impact of temperature on the effects of six mutations on sequence, structure, transcriptome, and organismal traits. We found temperature altered the transcriptomic response and key organismal traits such as growth rate and biofilm formation in a genotype-specific manner. Critically, mechanistic insights into the possible drivers of mutational effects emerged only when examining the relationships between different levels of organization: location of mutations in the tertiary structure and distance to key interacting molecules partly explained the observed transcriptomic differences, which in turn drove the impact of mutations on organismal traits. While falling short of capturing the full complexity of the system, our findings underscore the benefits of integrating insights across multiple biological levels to understand the relationship between environment and mutational effects in molecules with extensive pleiotropic effects.

Mutation↗

PubMed2026

Dietary Titanium Dioxide (E171) Alters the Colon Transcriptome-Evidence From a Human Dietary Intervention Study.

Food-grade titanium dioxide (E171) has been removed from the European food market due to concerns about its potential genotoxicity, yet human evidence remains limited. Given its continuous use outside the European Union, clarifying its potential hazard is essential for human risk assessment. In a randomized crossover study, 31 adults consumed 2 mg/kg body weight/day of E171 for 2 weeks, with biospecimens collected after both control and exposure periods. Oral intake resulted in elevated titanium concentrations in feces (CTRL: 6.3 mg/kg; E171: 377 mg/kg). Particle characterization showed a median size of 228 nm, with 9% <100 nm. Systemic oxidative stress increased, evidenced by increased superoxide radical levels in whole blood (p = 0.057). Transcriptomic profiling of colon biopsies revealed activation of 73 pathways linked to oxidative stress, cellular metabolism, and colorectal cancer-associated processes. The observed transcriptional changes were consistent with findings of its proposed mode of action. This human intervention study characterizes the effects of dietary E171 following human gastrointestinal digestion and provides evidence that exposure to dietary E171 induces systemic oxidative stress and transcriptional changes in the colon. These findings strengthen regulatory concerns about E171 as a food additive and its potentially harmful effects on human gastrointestinal health.

Humans↗

PubMed2026

Dynamic Alterations in the Blood Transcriptome Characterize Drug Use Behavior and Co-Morbidities in Cocaine Use Disorder: A Preliminary Study.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse that can benefit from multimodal treatment monitoring. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome are not only limited but also computationally complex. Therefore, we developed an analytical pipeline to investigate the connection between drug use behaviors during abstinence and change in the blood transcriptome. We conducted a longitudinal study with CUD (n = 12 subjects) and collected behavioral metrics and blood RNA-seq at baseline, 3, 6, and 9 months. Our analytical pipeline of the high-dimensional data encompasses hierarchical k-means clustering to classify subjects to responder groups based on behavioral scores and abstinence duration, in silico cell deconvolution, differential analysis with correlated multivariate testing over time, gene set enrichment analysis, and gene co-expression with time splines and RNA-seq data. The pipeline captured dynamic changes in behavioral scores and abstinence duration in responder groups. Genes showing differential transcript-level expression were enriched in substance use and cardiovascular disease-associated genetic risk loci in responder groups. Lastly, time-dependent gene co-expression revealed dynamic changes related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. This is a preliminary investigation, providing an innovative and scalable pipeline for blood-based longitudinal RNA-seq studies in CUD, potentially applicable to other substance use disorders. It outlines a data-driven approach for analyzing composite longitudinal drug use behavioral phenotypes with blood-based transcriptomics. We also demonstrate changes in drug use behaviors and the blood transcriptome during drug abstinence.

Humans↗

PubMed2025

Contribution of the Brain-Gut-Microbiome Axis to Intergenerational Abnormalities in a Rat Model of Perioperative Neurocognitive Disorder.

BACKGROUND: The brain-gut-microbiome (BGM) axis is a communication network through which the brain and gastrointestinal microbiota interact via neural, hormonal, immune, and gene expression mechanisms. Gut microbiota dysbiosis is thought to contribute to neurocognitive disorders, including perioperative neurocognitive disorder, and to various metabolic abnormalities. Recently, the authors reported that sevoflurane induces neurocognitive deficits in exposed rats as well as their future offspring, with male offspring being particularly affected (intergenerational perioperative neurocognitive disorder). In this study, the authors examined in the same animals whether the intergenerational effects of sevoflurane involve abnormalities in the BGM axis, and whether they are mitigated by paternal pretreatment with either the Na + -K + -Cl - (NKCC1) Cl - transporter inhibitor bumetanide or the glucocorticoid receptor inhibitor RU486, as previously demonstrated for neurocognitive deficits. METHODS: Male Sprague-Dawley rats (F0 generation) were exposed to 2.1% sevoflurane for 3 h on postnatal days 56, 58, and 60 (F0M_S group). Before each sevoflurane exposure, distinct experimental groups of F0 males received bumetanide (F0M_BS group) or RU486 (F0M_RS group). These males were mated on postnatal day 90 to produce offspring (F1 generation). Gut microbiota were profiled using 16S rRNA gene sequencing, and brain changes analyzed via RNA sequencing of hippocampal samples. RESULTS: F1 male offspring of F0M_S sires exhibited heightened corticosterone responses to stress, increased inflammatory markers, altered hippocampal transcriptomes, gut microbiota dysbiosis, elevated serum low-density lipoprotein cholesterol levels, and increased body weight. The only abnormality observed in F1 females was a shift in microbial diversity. F0M_S displayed profound alterations in hippocampal transcriptome, while microbial diversity was the only parameter affected in their gut microbiota. Bumetanide or RU486 mitigated most abnormalities, except increased body weight in F1 males. CONCLUSIONS: Paternal sevoflurane exposure in rats induces BGM axis abnormalities, particularly in male offspring, despite the absence of direct anesthetic exposure. Pretreatment with bumetanide or RU486 showed therapeutic efficacy.

Animals↗

PubMed2026

IL1RAP Is Associated With an Inflammation-Immunity-Related State in Skin Cutaneous Melanoma: Integrative Evidence From Pan-Cancer Data and Melanoma Immunotherapy Cohorts.

BACKGROUND: The crosstalk between inflammation and immunity plays a central role in tumor progression, immune evasion, and therapeutic response. Interleukin-1 receptor accessory protein (IL1RAP) is a key adaptor in inflammatory signaling, yet its immunological relevance and clinical implications in skin cutaneous melanoma (SKCM) remain largely unexplored. METHODS: We performed an integrative analysis combining pan-cancer and melanoma-focused datasets. Bulk transcriptomic, single-cell, spatial transcriptomic, genomic alteration, pharmacogenomic, and clinical survival data were obtained from TCGA, GTEx, GEO, ENA, and other public resources. IL1RAP expression was evaluated across cancer types in relation to diagnostic performance, immune subtypes, survival outcomes, functional pathway activity, immune-genomic states, somatic alterations, and drug-response metrics. Melanoma-focused analyses examined immune infiltration, methylation-derived tumor-infiltrating lymphocyte (MeTIL) scores, and exploratory survival associations in five treatment cohorts; the survival groups were defined using cohort-specific optimal cutoffs rather than median splits. RESULTS: IL1RAP expression differed between tumor and normal tissues in multiple cancers, although the direction and magnitude varied by cancer type. Pan-cancer survival associations were likewise context dependent. Single-cell and spatial transcriptomic resources indicated cell-type and spatial heterogeneity of IL1RAP expression within tumor microenvironments. Pathway, immune-genomic, and pharmacogenomic analyses identified exploratory associations with functional states, genomic features, and drug-response metrics. In SKCM, IL1RAP expression was associated with several immune-infiltration estimates and higher MeTIL scores. Across five melanoma immunotherapy cohorts, the direction and magnitude of the overall survival associations varied substantially. CONCLUSIONS: This retrospective integrative analysis suggests that IL1RAP may mark an inflammation-immunity-related state in SKCM. The heterogeneous associations across cancers and melanoma treatment cohorts support further validation but do not establish IL1RAP as a causal regulator, a treatment-response predictor, or a therapeutic target.

IL1RAP↗

PubMed2026

Transcriptomic landscape of microglia in mouse models of social dysfunction and oxytocin-mediated recovery.

Atypical sociability is a hallmark of neurodevelopmental disorders arising from genetic susceptibility and prenatal environmental perturbations that can affect diverse brain cell types. Using single-cell transcriptomics, we previously identified selective vulnerability of parvocellular oxytocin (OT) neurons in the paraventricular hypothalamus (PVH) following embryonic exposure to valproic acid (VPA), a teratogen that induces social deficits. Neonatal chemogenetic activation of OT neurons rescued these behavioral abnormalities and partially restored dysregulated gene expression. However, the effects of VPA exposure and OT neuron stimulation on non-neuronal PVH cells remained unclear. Here, we show that VPA induces transcriptional abnormalities in PVH microglia. Spatial transcriptomics revealed altered distributions of PVH microglial subtypes. Notably, neonatal OT neuron stimulation reversed a subset of VPA-induced microglial gene downregulation, while pharmacological manipulation of microglia normalized aberrant OT gene expression in putative parvocellular OT neurons. These findings support bidirectional OT neuron-microglia interactions that may underlie social dysfunction following embryonic VPA exposure.

autism spectrum disorder↗

PubMed2026

Low-salinity stress alters growth, histology, physiology, and transcriptomic profiles of the gills and antennal glands in Macrobrachium rosenbergii.

Salinity is a major abiotic constraint in freshwater aquaculture of the giant freshwater prawn Macrobrachium rosenbergii, yet the coordinated roles of the gills and antennal glands, the two primary osmoregulatory organs in decapod crustaceans, under low-salinity stress remain poorly characterized. Here, we integrated histological, physiological, and transcriptomic analyses to characterize the adaptive responses of M. rosenbergii to acute (96 h) and chronic (8 weeks) exposure to salinity 5. Chronic low-salinity stress significantly impaired growth performance and decreased the survival rate. Acute stress induced thinning of the gill filaments, partial disorganization of pillar cells, and dilation of the intermicrovillar space in the antennal glands, whereas chronic stress caused gill vacuolization, cuticle thinning, and adaptive folding of antennal gland microvilli. In parallel, acute exposure significantly decreased hemolymph sodium and potassium ion concentrations but increased magnesium ion concentration, whereas chronic exposure increased hemolymph sodium and potassium ion concentrations, upregulated gill Na+/K+-ATPase activity, and enhanced hepatopancreatic antioxidant capacity. Transcriptomic analyses revealed distinct tissue-specific responses. Under acute stress, the gills preferentially activated pathways associated with cytoskeletal remodeling, motor proteins, and tight junctions, whereas chronic acclimation shifted the transcriptional response toward the renin-angiotensin system and glutathione metabolism. In the antennal glands, acute stress rapidly activated the renin secretion pathway, whereas chronic exposure promoted membrane remodeling by enriching pathways related to lipid and glycan metabolism. These findings reveal tissue-specific functional differentiation and synergistic coordination between the gills and antennal glands that underpin M. rosenbergii's adaptive response to low-salinity stress.

Animals↗

PubMed2026

The ASH HematOmics Program supports integrative analysis of genomic and clinical data in hematologic diseases.

The increasing availability of genomic and transcriptomic sequencing has uncovered diverse genomic alterations and distinct gene expression profiles driving hematologic diseases, yet a data integration and sharing platform dedicated to hematology remains lacking. We developed the American Society of Hematology (ASH) HematOmics Program (ASHOP; ashop.hematology.org), a resource for exploring somatic alterations and gene fusions, transcriptomic results, and clinical data from 5960 patients spanning B-cell precursor and T-cell acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndromes, and chronic lymphocytic leukemia. Users can explore genomic alteration landscapes and comutation patterns via lollipop and matrix plots and analyze significantly altered genes in user-defined subcohorts. Transcriptomes can be explored through interactive uniform manifold approximation and projections, clustering, differential expression, and pathway enrichment. Genomic, transcriptomic features, and clinical outcomes can be correlated in a user-driven manner or combined to precisely define study cohorts. We illustrate the following 4 use cases of ASHOP: (1) stratification of DUX4-rearranged B-cell leukemias into Early/Multipotent and Committed subgroups with distinct outcomes, (2) characterization of HOXA/HOXB expression patterns in acute myeloid leukemias, (3) correlating mutational burden with mismatch repair deficiency and mutational signatures, and (4) investigation of TP53 alteration landscape. ASHOP is an open-access resource to inform genomic and transcriptomic data interpretation for hematologic malignancies and will expand to support additional diseases and data modalities from the ASH community.

Humans↗