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Results for “RNA-sequencing”

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At least 19 recordsLinked to original sources

PubMed2026

Transcriptomic analysis of eggs, rediae and cercariae reveal stage-specific adaptations in the rumen fluke Calicophoron daubneyi.

Rumen flukes, particularly the trematode Calicophoron daubneyi, are emerging parasites of livestock in Europe, yet transcriptomic insights into their environmental and intermediate host stages remain limited. Here, we present a comprehensive transcriptomic analysis of eggs at three distinct developmental stages (freshly excreted, early developmental and eye-spot stages), as well as rediae and cercariae, of C. daubneyi. High-quality RNA-sequencing (RNA-seq) datasets revealed both shared and stage-specific transcriptional profiles with each developmental stage exhibiting its own distinct expression pattern. Subsequent GO-Term enrichment analyses revealed that fully embryonated eggs in eye-spot-stage especially upregulated genes related to cilia assembly, movement and motility, reflecting preparation for miracidial hatching and host-seeking behavior. Rediae showed enhanced transcription of genes involved in diverse metabolic and biosynthetic processes, supporting rapid asexual proliferation within the snail intermediate host. Cercariae exhibited predominant upregulation of genes associated with signal transduction and energy metabolism, indicating the adaptation to its changing environmental conditions. These findings provide the first transcriptomic insights into the biology of C. daubneyi outside the definitive host, reveal molecular mechanisms underlying development, transmission and adaptation to a changing environment and identify stage-specific genes as potential targets for interventions aimed at disrupting the parasites life cycle and controlling rumen flukes in the future.

Animals↗

PubMed2026

Immune-Like Malignant Epithelial Programs Shape Tumor-Immune Interactions and Inform Prognostic Stratification in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is characterized by marked cellular heterogeneity, yet how malignant epithelial states contribute to immune regulation and clinical outcomes remains incompletely defined. We integrated single-cell RNA-sequencing data to map the cellular landscape of LUAD and identify malignant epithelial cells based on inferred copy-number alterations. Epithelial states were further examined through trajectory inference, transcription factor analysis, and cell-cell communication profiling. Single-cell-derived genes were subsequently integrated with TCGA and independent GEO cohorts to construct and validate a machine learning-based prognostic signature. Malignant epithelial cells displayed distinct functional programs, including an immune-like state associated with genomic instability, immune-related transcriptional activity, tumor-immune communication, and patient outcomes. The resulting immune-like malignant epithelial cell signature (IMEC-Sig) consistently stratified survival across multiple cohorts. Low IMEC-Sig scores were accompanied by greater immune infiltration, higher immune checkpoint expression, and increased immunophenoscore, whereas high scores were linked to a comparatively immunosuppressive phenotype. Pan-cancer analyses further identified KRT8 as a gene associated with unfavorable prognosis, and functional experiments showed that KRT8 silencing suppressed proliferation, migration, invasion, and colony formation in LUAD cells. Together, these findings connect malignant epithelial heterogeneity with the immune context and clinical outcomes, support IMEC-Sig as a biologically informed prognostic tool, and nominate KRT8 as a potential therapeutic target in LUAD.

Humans↗

PubMed2026

Age-Associated Four-Gene Prognostic Signature in Breast Cancer.

BACKGROUND: Young-onset breast cancer is associated with inferior disease-free survival (DFS), but the contribution of additional molecular heterogeneity remains unclear. AIMS: To identify an exploratory age-associated gene expression signature linked to recurrence-related outcomes and evaluate its prognostic association. METHODS AND RESULTS: We analyzed clinicopathological and RNA-sequencing data from 821 patients with Stages I-III invasive ductal or lobular carcinoma in The Cancer Genome Atlas, including 142 patients aged ≤ 45 years. Genes associated with both age and DFS were screened, followed by LASSO-Cox and stepwise multivariable Cox regression. A four-gene signature (Sig4: C4orf14 [NOA1], LINC01124, ZNF704, and AGFG2) was identified. Young patients had significantly worse DFS than older patients, whereas overall and disease-specific survival did not differ significantly. After adjustment for clinicopathological factors, young age remained associated with worse DFS. Following inclusion of the continuous Sig4 score, the age association was attenuated and no longer statistically significant, while Sig4 remained independently associated with worse DFS. Sig4-high tumors were enriched for proliferation, cell-cycle, DNA-repair, metabolic, and stress-response pathways. In METABRIC, the fixed TCGA-derived Sig4 score was associated with worse relapse-free survival in the overall cohort but not in patients aged ≤ 45 years. CONCLUSION: Sig4 is an exploratory age-associated four-gene signature with potential general prognostic relevance in breast cancer. Its utility for risk stratification specifically in young-onset breast cancer was not externally validated and requires confirmation in independent prospective cohorts enriched for young patients.

Humans↗

PubMed2026

Recent advancements in exosomal content analysis: the future of liquid biopsy.

Exosomes are widely acknowledged as an essential agent that carries biomarkers for specific diseases, representing the molecular status of their parent cells and providing extremely useful diagnostic insights. They can be isolated from different body fluids and contain a range of cargo molecules, including proteins, lipids, metabolites, and nucleic acids. Recent advancements in technology have greatly accelerated exosome research. Proteomics provides protein signatures linked to many pathological conditions, enabling quick and clinically scalable diagnostic tools, whereas high-throughput RNA-sequencing can be used to perform detailed transcriptome profiling. Exosomal biomarkers are showing promising clinical results in early detection of neurological diseases, infectious and cardiovascular disorders, oncology, and other medical conditions, hence accelerating therapeutic monitoring. Despite these advances, several challenges continue to hinder clinical translation including the lack of standardized isolation protocol, variability in exosome yield and purity, biological heterogeneity, and limited large-scale clinical validation. Addressing these limitations will be critical for the successful integration of exosome-based liquid biopsy into routine clinical practice. Overall, exosomes having significant potential as diagnostic tool, represent a transformative horizon in biomedical liquid biopsy research to redefine the landscape of less-invasive diagnostics and tailored clinical applications.

Humans↗

PubMed2026

RBFOX3 regulates hippocampal transcriptomic programs to maintain synaptic and ultrastructural integrity.

RBFOX3 is a neuron-specific RNA-binding protein essential for maintaining brain circuit homeostasis and functional connectivity. Genetic disruptions in RBFOX3 are clinically linked to cognitive impairment, epilepsy, and sleep disorders. Although global Rbfox3 knockout (Rbfox3-/-) mouse models have established its necessity in hippocampus-dependent neuronal circuits and behaviors, the underlying hippocampal transcriptomic landscape and synaptic ultrastructure remain poorly understood. To address these gaps, we integrated hippocampal RNA-sequencing from Rbfox3-/- mice with high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation analysis. We identified 3,401 differentially expressed genes in the hippocampus of Rbfox3-/- mice, confirming 1,920 as candidate RBFOX3 targets. Gene Ontology enrichment analysis revealed that these candidate targets converge on pathways governing neuronal morphogenesis, synaptic transmission, dendritic development, and cognition. Furthermore, transmission electron microscopy of the hippocampal dentate gyrus revealed that while the overall presynaptic area remained unaltered, Rbfox3 deletion reduced presynaptic vesicle number, presynaptic mitochondria area, and postsynaptic density thickness. Collectively, our findings demonstrate that RBFOX3 acts as a critical regulator orchestrating the transcriptomic programs required for hippocampal structural and functional maturation, revealing that its loss compromises both the metabolic and structural architecture of the synapse.

Hippocampus↗

PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗

PubMed2026

Genome-wide association study reveals two novel genetic loci associated with chronic lung allograft dysfunction.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) leads to declining respiratory function and high mortality, representing the main barrier to long-term survival in lung transplantation (LT). We performed the first genome-wide association study (GWAS) investigating donor's and recipient's genetic factors associated with CLAD. METHOD: We genotyped 392 donor-recipient pairs from the multicentric Cohort in Lung Transplantation. We tested 4.5 million SNPs for association with CLAD using multivariable logistic regression models corrected for age, sex, initial disease and genetic ancestry. Three levels of explanatory variables were separately considered to conduct GWAS: donors-only, recipients-only, and donor-recipient mismatches. We also ran HLA-centric analyses using the same models. RESULTS: Our analysis confirmed the deleterious impact of HLA allelic and epitopic mismatches on CLAD risk, mostly driven by class I HLA (p=0.004). No significant associations with CLAD were found for donors' genotypes or donor-recipient non-HLA mismatches. We highlighted two independent recipient's loci associated with CLAD, including one protective signal (0.39 in CLAD vs 0.66 in non-CLAD recipients, p-value=5.05×10-7, q-value=0.017, OR=0.35) encompassing the PLXDC2 gene, and one risk signal (0.66 in CLAD vs 0.38 in non-CLAD recipients, p-value=9.86×10-7, q-value=0.017, OR=2.83) encompassing the ZNF518A/BLNK genes. These non-coding SNPs are putative regulatory variants of gene expression. Importantly, our single-cell RNA-sequencing showed a down-regulation of PLXDC2 in fibroblasts and lung epithelium in CLAD vs healthy controls. CONCLUSION: This first LT GWAS revealed two candidate loci from the recipient's genome, both biologically relevant for CLAD pathogenesis. Our study calls for larger LT genomic initiatives to increase power for signal discovery.

Humans↗

PubMed2026

Anti-inflammatory and phosphorylation effects of CFTR modulator triple therapy in cystic fibrosis.

CFTR modulators like elexacaftor-tezacaftor-ivacaftor (ETI) improve morbidity in cystic fibrosis (CF), but their systemic effects on young children are not yet clear. We hypothesize that ETI has anti-inflammatory effects and reverse disease-associated molecular signatures in children with CF. This exploratory pilot study evaluates the cellular mechanisms of ETI on peripheral immune cells in children (<12 years) with CF using a multi-omics approach. Seventeen children with CF (median age 8.7 years, 26% female) and 12 controls (median age 9.6 years, 42% female) were included for blood RNA-sequencing, proteomics and phosphoproteomics. Baseline pathway enrichment analysis revealed systemic inflammation, transmembrane transporter deficiencies, reduced protein kinase, and GTPase activity. Three months post-ETI, anti-inflammatory effects, epigenetic modulation, and increased protein kinase activity were observed, indicating partial reversal of cellular abnormalities. ETI modified systemic inflammatory, epigenetic, and phosphorylation pathways in young children with CF, offering insights into CF pathology and potential biomarkers for treatment monitoring.

cystic fibrosis↗

PubMed2026

A machine learning-derived and functionally validated circadian rhythm signature predicts clinical outcomes and in silico drug sensitivity in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) displays considerable heterogeneity in clinical outcomes, highlighting the need for reliable prognostic biomarkers. While the aberrant expression of circadian rhythm-related genes has been implicated in cancer pathogenesis, its comprehensive role in CRC progression and predicted therapeutic vulnerabilities remains inadequately characterized. METHODS: Bulk and single-cell RNA-sequencing data were integrated from multiple CRC cohorts. A circadian rhythm signature (CRS) was developed through machine learning algorithms and validated for prognostic value. Comprehensive analyses of tumor microenvironment, genomic alterations, and drug sensitivity were performed. Furthermore, the biological function of the core gene, BHLHE40, was validated in CRC cell lines through CCK-8, EdU, and wound healing assays. RESULTS: Single-cell analysis demonstrated an elevated expression signature of circadian rhythm-related genes in dendritic cells. The optimized CRS, comprising 14 circadian rhythm-related genes, successfully categorized patients into high- and low-risk groups. Patients with a high CRS showed markedly poorer overall survival and computationally inferred immunosuppressive features, including reduced CD8+ T cell infiltration and increased M2 macrophage polarization. Genomic analysis revealed enhanced mutation burden in TP53 and alterations in RTK-RAS/WNT pathways. Notably, in vitro assays confirmed that BHLHE40 is significantly overexpressed in CRC cells. Knockdown of BHLHE40 markedly inhibited tumor cell proliferation and migration. Drug sensitivity profiling identified bexarotene and SMER-3 as potential therapeutic options for high-CRS patients. A nomogram integrating CRS with clinical parameters demonstrated superior predictive accuracy for 1-, 3-, and 5-year survival. CONCLUSIONS: The CRS represents a promising prognostic biomarker that reflects tumor immune status and genomic features, providing valuable insights for personalized treatment strategies in CRC.

Circadian rhythm↗

PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗

PubMed2026

The establishment of prostate-specific, SKP2 humanized mice by CRISPR knock-in method reveals neoplastic initiation and microenvironmental reprogramming.

Genetic inactivation of SKP2 has been shown to effectively prevent cancer initiation and block tumorigenesis. However, direct in vivo evidence for SKP2 on cancer initiation and prostatic microenvironment is still lacking and a SKP2 humanized mouse model is critical for developing prostate cancer immunoprevention approaches through targeting SKP2. We therefore have established a prostate-specific human SKP2 knock-in mouse model driven by an endogenous mouse probasin promoter. Overexpression of hSKP2 induces PIN and low-grade carcinoma. RNA-sequencing analysis revealed significant gene expression alterations in EMT, extracellular matrix, and interferon signaling. Single-cell deconvolution showed an increase of fibroblast population and a decrease of CD8+ T cell and B cell populations. Consistent with these results from the SKP2 humanized mouse, SKP2 protein is overexpressed in human prostatic hyperplasia, PIN and prostate adenocarcinoma compared to normal prostate tissues. Overexpression of SKP2 markedly increased cell migration and invasion and induced the gene expression of EMT and interferon pathways. Inhibition of SKP2 signaling by Flavokawain A and C1 reverses EMT and affects EMT and interferon-related gene expression. In addition, paired prostate organoids were derived from SKP2 humanized and wild-type mice for drug screening and validated by known SKP2 inhibitors, Flavokawain A and C1. Both of which selectively decreased viability and altered the morphologies of organoids of hSKP2 knock-in rather than wild-type mice. Our studies provide a well-characterized prostate-specific hSKP2 knock-in mouse model and offer new mechanistic insights for understanding the oncogenic role of SKP2 in shaping the prostatic microenvironment during early carcinogenesis.

Animals↗

PubMed2026

Decoding the landscape of cell-type-specific co-expressed transcription factors in soybean.

Soybean (Glycine max) is an essential source of protein and oil with high nutritional value for human and animal consumption. To enhance our understanding of soybean biology, it is essential to have accurate information regarding the expression of each of its protein-coding genes. Here, we present Tabula Glycine max, a soybean single-cell resolution transcriptome atlas. This atlas comprises single-nucleus RNA-sequencing data from ten different G. max organs and morphological structures constituting the entire soybean plant. These nuclei are grouped into 156 different clusters based on their transcriptomic profiles. The breadth of various organs, tissues and cell types represented in Tabula Glycine max reveals that the pattern of co-expressed transcription factor genes is sufficient to define most cell types based on their function and organ of origin. Defining cell-type-specific co-expressed transcription factor genes offers a new perspective to engineer cell-type-specific programmes and enhance the biology of unique soybean cell types. This cellular resolution and breadth make the Tabula Glycine max an exceptional resource for the plant and soybean communities.

Journal Article↗

PubMed2026

REACTOR: REgulon Activity analysis and Comparison Tool for single-cell transcriptOmics Research.

SUMMARY: We introduce REACTOR, a computational tool designed to detect differential activity of transcriptional regulators and their target genes (regulons) in single-cell RNA-sequencing data. It expands the currently available framework for regulon analysis by introducing a robust statistical test to detect differential regulon activity between conditions, such as disease versus control, with multiple replicates. By contrasting different conditions, REACTOR enables identification of key condition- and cell type-specific regulons. To demonstrate the use of REACTOR, we illustrate its performance in a publicly available COVID-19 dataset. AVAILABILITY: REACTOR R-package together with an implementation vignette are available at https://www.github.com/elolab/REACTOR.

Regulon↗

PubMed2026

Mapping the causal chain from genetic risk variants to lipid dysmetabolism in Parkinson's disease.

The molecular pathways linking genetic variants to Parkinson's disease (PD) onset and progression remain incompletely defined; however, risk alleles in multiple genes, including GBA1, strongly implicate lipid metabolism. To systematically identify causal biomarker signatures, we analysed comprehensive metabolome profiles from blood plasma in 149 PD patients and 150 controls, along with complementary genetic, RNA-sequencing and metabolic data from other available clinical and pathologic cohorts. Using colocalization and summary-data-based Mendelian randomization, we tested whether expression and metabolic quantitative trait loci mediate the association between implicated genetic variants and PD risk. We further integrated differential metabolomics and proteomics from blood and brain to reveal pertinent mechanisms. We show that common PD risk variants at the serine palmitoyltransferase small subunit B (SPTSSB) locus, a key regulator of de novo sphingolipid biosynthesis, are associated with increased SPTSSB brain expression and elevated plasma ceramides. Additional analyses strongly support our hypothesis that a common SPTSSB causal variant is responsible for PD risk as well as the expression and metabolic quantitative trait loci. Multiple sphingolipids and fatty acid derivatives were perturbed in PD, and we identified both unique and shared features with the Alzheimer's disease metabolome. A PD acylcarnitine signature was further replicated in human post-mortem brain tissue, when comparing those with or without preclinical Lewy body pathology. Integrated analysis of complementary brain proteomic profiles revealed dysregulation of mitochondrial processes dependent on acylcarnitines, including fatty acid beta-oxidation, the tricarboxylic acid cycle and oxidative phosphorylation. Our results identify promising biomarkers and reveal a causal chain linking genetic variation to altered gene/protein expression, lipid dysmetabolism, and the manifestation of PD.

Humans↗

PubMed2026

Immature Neutrophil Programs Associate With Burn Mortality and Extend Across Critical Illnesses.

Severe burns provoke a systemic "genomic storm," yet cell states associated with divergent outcomes remain unclear. We profiled blood cells by single-cell RNA-Sequencing (73 014 cells) from adult patients with burn injuries within postburn day 17 (n = 4) and healthy donors (n = 5), integrated data with bulk signatures of burn size, inhalation injury, and mortality, and evaluated clinical associations in the American Burn Association National Burn Repository. Burn was associated with emergency hematopoiesis marked by expansion of hematopoietic stem/progenitor-like cells, immature neutrophils, and plasmablast/plasma cell states, alongside depletion of naïve CD4+/CD8+ T cells and dendritic cells. Larger burns (>20% TBSA) showed enrichment of humoral transcriptional programs, including plasmablast/plasma cell activation and suppression of cytotoxic CD8+ T-cell states. In multivariable models, inhalation injury was a stronger predictor of death (adjusted odds ratio [OR] 1.9) than burn size (adjusted OR 1.1) and shared greater overlap with the most perturbed single cells in non-survivors; 55% of co-perturbed cells were neutrophils, implicating granulocyte dysregulation as a common lethal axis. We identified a neutrophil-specific 5-gene panel (OLFM4, RETN, LCN2, ARG1, and BTNL3) that discriminated survivors vs non-survivors after burns (area under the curve [AUC] > 0.9) and generalized to trauma (n = 158; AUC 0.81) and intensive care unit COVID-19 (n = 103; AUC 0.75), providing information orthogonal to conventional biomarkers and severity scores. Cytomorphology corroborated transcriptomic immaturity, with ~2-fold higher band neutrophils and larger neutrophil size in a fatal case. Computational drug-reversal analysis highlighted galectin-1 inhibition as a candidate modulator of mortality-associated neutrophil programs. Together, our findings suggest that immature neutrophils represent a shared immune feature across severe burns and other forms of critical illness.

Humans↗

PubMed2026

Tissue-Level Transcriptomic Entropy Reveals Organ-Specific Aging Patterns and Predicts Cancer Progression.

Although aging and cancer share complex molecular mechanisms, distinguishing causative factors from byproducts remains challenging. Here, we investigated the role of tissue transcriptomic entropy-a measure of transcriptional disorder-in aging and cancer processes by analyzing RNA-sequencing data from over 25,000 samples from human and mouse tissues. We found that entropy changes during aging are highly tissue-specific, with some tissues showing increased entropy while others exhibit decreased or stable entropy levels. Moreover, transcriptomic entropy strongly correlates with age-related processes, showing positive associations with proliferation, cellular senescence, somatic mutation burden, and cellular reprogramming, whereas it negatively correlates with stemness. In cancer, we observed that primary tumors generally display higher entropy than normal tissue, with its levels further increasing in metastatic stages. Cancer treatment modulated entropy patterns in multiple contexts, with changes suggesting a role for transcriptional complexity in tumor plasticity and therapy resistance. Elevated entropy levels predicted poor survival outcomes in multiple cancer types, suggesting its potential as a prognostic marker. Furthermore, differential expression analysis revealed that entropy-associated genes are enriched in developmental processes and depleted in metabolic pathways, indicating a possible link to cellular dedifferentiation. Finally, we found increased entropy in various age-related disorders beyond cancer, suggesting that transcriptomic entropy may be a common feature in age-related diseases. Our findings establish transcriptomic entropy as a fundamental parameter in aging and cancer progression, offering new insights into disease mechanisms.

Humans↗

PubMed2026

Comparative Transcriptomic Analyses Identify Candidate Genes for Convergent Reproductive Shifts in a Bimodal Viviparous Amphibian.

Shifts in reproductive mode represent key evolutionary innovations that shape species' life histories and evolutionary trajectories. Species showing bimodal reproductive strategies with multiple independent origins offer a rare opportunity to gain insights into the adaptive processes and mechanisms underlying convergent traits. The fire salamander, Salamandra salamandra, is the only amphibian exhibiting intraspecific variation in reproductive mode across multiple independent reproductive shifts, enabling investigation of the transition between larviparity (females give birth to aquatic larvae) and pueriparity (females give birth to fully developed terrestrial juveniles) within a single species and across different timescales. Pueriparity is an adaptive innovation that skips the aquatic larval stage, allowing individuals to exploit habitats with no available water bodies. The fire salamander is larviparous across most of its range, but pueriparity has evolved independently at least three times: once in the early Pleistocene within S. s. bernardezi in the mountains of northern Spain, and more recently on two land-bridge islands (NW Spain) inhabited by S. s. gallaica. To identify candidate genes associated with these distinct reproductive modes, we compared gene expression profiles of the uterus and oviduct of pregnant females across two independent evolutionary transitions using RNA-sequencing. We detected shared changes in maternal gene expression among pueriparous S. s. bernardezi and S. s. gallaica relative to their larviparous counterparts, in addition to differences unique to each independent evolutionary transition. Functional enrichment analyses indicated that differentially expressed genes were associated with reproductive timing, angiogenesis, and maternal signalling, consistent with the phenotypic differences observed in the uterine environment and embryonic development between the two reproductive modes. This study represents an important first step towards understanding the genomic basis of the evolution of pueriparity in a remarkable bimodal reproductive system, and provides transcriptomic resources and candidate genes for future research into the genomic architecture underlying this poorly understood adaptive trait.

Animals↗

PubMed2026

Thalamic NRXN1-mediated input to human cortical progenitors drives excitatory neurogenesis.

The human cerebral cortex develops through coordinated signals from within the cortex and from other brain regions, including the thalamus. However, how thalamic neuronal projections influence early human cortical development remains less well-understood. In this study, we fused cortical and thalamic organoids to investigate how thalamic input shapes the maturation of human cortical cells. Using single-nuclei RNA-sequencing and cellular imaging, we found that thalamic input increases the production of cortical excitatory neurons. We identify neurexin-1 (NRXN1) as a mediator of physical contact between thalamic axons and cortical outer radial glia. Genetic knockout of thalamic NRXN1 reduced these contacts and attenuated the production of upper-layer excitatory neurons. These findings reveal a mechanism by which thalamic input regulates human cortical progenitors and shapes excitatory neuron production during development.

Animals↗