Biology subjects

Nakayama, T.

Publications and source records attributed to Nakayama, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Evolution of form I-related RuBisCOs updated: Uncertainties and diversity encompassing Bacteria and Archaea.

Forms I&prime, I&Prime, and I RuBisCOs were recently identified in bacterial metagenome-assembled genomes (MAGs) and are significant for evolutionarily bridging form I, which is responsible for the major part of carbon fixation on Earth, and other forms. Pioneering studies focused mainly on the biochemical and structural characteristics of "form I-related" RuBisCOs and deduced the evolution of this protein family over phylogenetic relationships among form I and form I-related sequences. We here surveyed form I-related sequences in public databases and conducted phylogenetic analyses incorporating the updated diversity of form I-related RuBisCOs. This study yielded two major outcomes regarding RuBisCO evolution. First, the analyses presented here suggest uncertainties overlooked in the previously published studies. It appeared to be difficult to conclude (i) the phylogenetic relationship among forms I, I&prime, and I&Prime, (ii) the monophyly of form I&prime, or (iii) the monophyly of form I. Second, we identified a gene encoding form I RuBisCO in an archaeal MAG, and this protein is likely involved in the pentose bisphosphate pathway. The results presented here suggest that the evolutionary route leading to form I in RuBisCO evolution remains unsettled.

evolutionary biology↗

bioRxiv2026

Leptin receptor deficiency suppresses gastric tumorigenesis by limiting stromal activation and tumor microenvironment development.

Leptin receptor (LEPR) signaling has been implicated in multiple malignancies; however, its role in gastric tumors remains poorly defined. We previously demonstrated that mice with gastrointestinal epithelial cell-specific deletion of suppressor of cytokine signaling 3 (SOCS3 cKO), a negative feedback regulator of LEPR signaling, develop gastric tumors due to aberrant leptin production and LEPR activation. Here, we demonstrate that concurrent deletion of both Socs3 and Lepr (double knockout; DKO) under the same promoter substantially suppresses gastric tumorigenesis and markedly prolonged survival. Whereas SOCS3 cKO mice exhibited early stromal activation, increased TGF-{beta}1 production, accumulation of cancer-associated fibroblasts (CAFs) and collagen deposition, these tumor-promoting alterations were substantially attenuated in DKO mice. Additionally, DKO mice showed reduced inflammatory cytokine and chemokine signaling, decreased the accumulation of Gr-1+CD11b+ myeloid-derived suppressor cells, and reduced LEPR and TGF-{beta} signaling. Analysis of The Cancer Genome Atlas stomach adenocarcinoma cohort revealed high LEPR expression in the chromosomal instability and genomically stable subtypes, correlating with poor prognosis. Moreover, LEPR expression was mutually exclusive with CLDN18 and ERBB2, two major therapeutic biomarkers, and positively correlated with a CAF-related transcriptional signature. Our findings identify LEPR signaling in epithelial cells as a key driver of gastric tumorigenesis through promotion of stromal activation and tumor microenvironment development. They further highlight LEPR as a promising therapeutic target for patients with gastric cancer who are unlikely to benefit from current ERBB2/HER2- or CLDN18-directed therapies.

cancer biology↗

bioRxiv2026

Upregulation of Calbindin in Adult Inhibitory Neurons Reactivates Critical Period Plasticity in Mouse Visual Cortex

Critical periods are windows of peak learning performance where heightened synaptic plasticity enables fast, robust reorganization in juvenile brain circuits. Unlike adult plasticity which requires ongoing, persistent change in sensory experience, cortical representations can be rapidly changed during critical periods and have enduring effects. Transplantation of GABAergic inhibitory neurons has been shown to restore critical period plasticity to recipient circuits by triggering signalling changes within host inhibitory neurons. Here we transcriptionally profiled host inhibitory neurons in mouse primary visual cortex (V1) to detect gene expression changes during transplant-induced plasticity. Gene ontology enrichment analysis of differentially-expressed (DE) transcripts in host inhibitory neurons revealed synaptic plasticity- and inhibitory neuron development-related profiles. We assessed the protein expression of a top DE candidate, the calcium-binding protein Calbindin (Calb1), across transplant conditions and developmental stages. We found high Calb1 expression during the V1 critical period and during transplant-induced plasticity. To assess the functional significance of transplant-reactivated DE gene activity on visual cortical plasticity, we developed a set of AAVs to manipulate Calb1 expression specifically within inhibitory neurons. Using intrinsic signal imaging to measure ocular dominance plasticity, we found that Calb1 levels in V1 inhibitory neurons determine the extent of visual cortical plasticity. Our study provides evidence that direct induction of critical period-stage gene expression patterns in inhibitory neurons restores juvenile plasticity in targeted adult cortical circuits.

neuroscience↗

bioRxiv2026

Coordinated immune-epithelial dynamics in the nasal epithelium protect against respiratory virus infection

Epithelial remodeling is a hallmark of host antiviral responses that strengthen barrier defenses against infection. Our current understanding of viral pathophysiology within the nasal epithelium, the initial site of most respiratory viral infections, remains incomplete due to limited understanding of the native tissue architecture and protective epithelial remodeling during immune events. Leveraging coronavirus disease 2019 (COVID-19) as a model, we applied spatial multi-omics on nasal cross-sectional tissues to characterize the immune-epithelial landscape during infection, identifying a coordinated increase in goblet cells and suppressive macrophages associated with elevated IL13 in the immune compartment. Our results further reveal that goblet cell and suppressive macrophage enrichment are spatially linked in proximity to IL13-expressing CD4 T cells, consistent with IL13-driven remodeling in situ. Using a primary human nasal air-liquid interface model, we demonstrate that IL13 alone is sufficient to remodel epithelial composition and morphology, subsequently restricting viral infection by reshaping the apical mucus barrier of the nasal epithelium. Our findings uncover a spatially organized, IL13-driven circuit for immune-epithelial remodeling as a protective barrier against respiratory viral infections.

immunology↗

bioRxiv2026

Biosensor Cell Array Reveals Temporal GABA Secretion Dynamics from Pancreatic Islets

Pancreatic beta cells have the unique function of synthesizing and secreting high amounts of the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA). The mechanism of GABA secretion, whether vesicular or channel-mediated, is debated. Our study reveals surprising temporal complexity in the pattern of islet GABA secretion. We used insulin secretion modulators to demonstrate that GABA release is not directly correlated with insulin secretion. VGAT reporter mice also showed that beta cells do not express the requisite vesicular GABA transporter (VGAT) for vesicular GABA release. Instead, GABA is secreted from the cytosol in pulses by the LRRC8A/D isoform of the volume regulatory anion channel (VRAC). We further demonstrate the dynamic coordination of GABA release with calcium influx in beta cells and dependence on beta cell depolarization. These results suggest a model where GABA is released during the peaks of beta cell calcium oscillations to provide feedback which strengthens and reinforces the oscillation waveform.

physiology↗

bioRxiv2026

Population genomics reveal genetic variants associated with lunar-regulated spawning time in grass puffer

High and low tides occur twice a day (every [~]12.4 hours), with the largest tidal ranges during spring tides around new and full moons (every [~]14.765 days). Although lunar cycles shape diverse animal phenotypes, particularly the reproduction of coastal animals, the genetic basis of lunar-related rhythms remains unclear. Since phenotypic variation is a valuable resource for elucidating such mechanisms, we examined geographic variation in the lunar-regulated mass spawning of the grass puffer (Takifugu alboplumbeus) along the Japanese coast. Western populations spawned during the first half of the spring tides, whereas eastern populations spawned during the second half. Furthermore, the spawning was restricted to a narrow daily time window that occurred earlier in the western populations than in the eastern ones. Assuming that spawning is regulated by circadian gating, this geographic shift in the daily spawning window could account for the population difference in semilunar spawning timing. Consistent with this hypothesis, the free-running circadian period ({tau}), which can affect the phase of the gating window, was shorter in the western populations. Mathematical modeling recapitulated the observed geographic difference in the spawning time window based on variation in {tau}. To identify candidate genes responsible for these differences, we conducted population genomics analysis and identified proline-rich transmembrane protein 1-like (prrt1l) as a candidate. Expression of prrt1l was observed in the circadian pacemaker suprachiasmatic nucleus, and triple CRISPR F0 knockout of prrt1l shortened the free-running period in larvae. These findings suggest a potential mechanism underlying the geographic variation in lunar-synchronized spawning behavior. HighlightsO_LIThe geographic variation exists in the lunar-regulated spawning of the grass puffer, with differences in spawning dates and times between western and eastern Japan. C_LIO_LIThe free-running period of western populations is shorter than that of eastern populations, which is consistent with their earlier spawning timing. C_LIO_LIPopulation genomics analysis identified prrt1l as a candidate gene harboring population-specific missense mutations, the knockout of which shortens the free-running period. C_LI

evolutionary biology↗

bioRxiv2025

Phylogenetic dissection provides insights into the incongruity in the tree of Archaeplastida between the analyses of nucleus- and plastid-encoded proteins.

Archaeplastida is defined as a taxonomic assemblage comprising three sub-clades, namely Chloroplastida, Glaucophyta, and Rhodophyta plus two non-photosynthetic lineages sister to Rhodophyta (the latter three lineages collectively termed "Rhodozoa" here). The members of Archaeplastida are the descendants of the eukaryote that took up and transformed a cyanobacterial endosymbiont into a primary plastid. Recent phylogenetic analyses of multiple proteins (phylogenomic analyses) stably recovered the monophyly of Archaeplastida, but uncertainty remains in the relationship among the three sub-clades in this assemblage. The phylogenomic analyses of nucleus-encoded proteins (nuc-proteins) grouped Chloroplastida and Glaucophyta together, excluding Rhodozoa in the Archaeplastida clade, albeit the union of Chloroplastida and Rhodophyta was often inferred from the phylogenomic analyses of plastid-encoded proteins (pld-proteins). In this study, we challenged the previously recognized but as-yet-explicitly addressed issue in the tree of Archaeplastida (ToA). The detailed analyses of the nuc-protein and pld-protein supermatrices revealed that taxon sampling can invoke different types of phylogenetic artifacts into the inferences from both supermatrices examined here. In the end, we propose a working hypothesis for the ToA and provide future perspectives toward resolving the ToA.

evolutionary biology↗

bioRxiv2025

A cellular entity retaining only its replicative core: Hidden archaeal lineage with an ultra-reduced genome

Defining the minimal genetic requirements for cellular life remains a fundamental question in biology. Genomic exploration continually reveals novel microbial lineages, often exhibiting extreme genome reduction, particularly within symbiotic relationships. Here, we report the discovery of Candidatus Sukunaarchaeum mirabile, a novel archaeon with an unprecedentedly small genome of only 238 kbp --less than half the size of the smallest previously known archaeal genome-- from a dinoflagellate-associated microbial community. Phylogenetic analyses place Sukunaarchaeum as a deeply branching lineage within the tree of Archaea, representing a novel major branch distinct from established phyla. Environmental sequence data indicate that sequences closely related to Sukunaarchaeum form a diverse and previously overlooked clade in microbial surveys. Its genome is profoundly stripped-down, lacking virtually all recognizable metabolic pathways, and primarily encoding the machinery for its replicative core: DNA replication, transcription, and translation. This suggests an unprecedented level of metabolic dependence on a host, a condition that challenges the functional distinctions between minimal cellular life and viruses. The discovery of Sukunaarchaeum pushes the conventional boundaries of cellular life and highlights the vast unexplored biological novelty within microbial interactions, suggesting that further exploration of symbiotic systems may reveal even more extraordinary life forms, reshaping our understanding of cellular evolution. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=123 SRC="FIGDIR/small/651781v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@f5fbd6org.highwire.dtl.DTLVardef@168bee5org.highwire.dtl.DTLVardef@1ccb02forg.highwire.dtl.DTLVardef@14315fa_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2025

Inverse signal importance in real exposome: How do biological systems dynamically prioritize multiple environmental signals?

Living organisms integrate multiple signals from their exposome, the totality of environmental influences experienced throughout life, to adapt to complex, non-stationary environments. While organisms are thought to flexibly prioritize relevant signals depending on context, its regulatory mechanisms remain largely unknown. Laboratory studies with precisely controlled conditions fail to capture this adaptability by isolating organisms from the complex exposome. Here, we developed a machine learning framework, Inverse Signal Importance (ISI), to infer how organisms prioritize external signals from time-series data of environmental factors and physiological responses. We applied ISI to analyze gonadal development in medaka fish under natural outdoor conditions, tracking gonadosomatic index alongside environmental signals including water temperature, day length, and solar radiation over two years. Our analysis revealed that signal importance levels exhibit complex dynamics distinct from simple environmental periodicity and correlates significantly with specific gene expression patterns. Notably, genes associated with temperature-related signal importance display differential expression between outdoor and controlled laboratory conditions, suggesting their role in environmental adaptation. These findings indicate that ISI effectively captures latent physiological dynamics in adaptation of exposome. By decomposing biological responses into deterministic and adaptive components, ISI provides a novel approach to uncover mechanisms of organismal adaptation in natural environments.

bioinformatics↗

bioRxiv2025

Multi-omic analysis of the ciliogenic transcription factor RFX3 reveals a role in promoting activity-dependent responses via enhancing CREB binding in human neurons

Heterozygous loss-of-function (LoF) variants in RFX3, a transcription factor known to play key roles in ciliogenesis, result in autism spectrum disorder (ASD) and neurodevelopmental delay. RFX binding motifs are also enriched upstream of genes found to be commonly dysregulated in transcriptomic analyses of brain tissue from individuals with idiopathic ASD. Still, the precise functions of RFX3 in the human brain is unknown. Here, we studied the impact of RFX3 deficiency using human iPSC-derived neurons and forebrain organoids. Biallelic loss of RFX3 disrupted ciliary gene expression and delayed neuronal differentiation, while monoallelic loss of RFX3 did not. Instead, transcriptomic and DNA binding analyses demonstrated that monoallelic RFX3 loss disrupted synaptic target gene expression and diminished neuronal activity-dependent gene expression. RFX3 binding sites co-localized with CREB binding sites near activity-dependent genes, and RFX3 deficiency led to decreased CREB binding and impaired induction of CREB targets in response to neuronal depolarization. This study demonstrates a novel role of the ASD-associated gene RFX3 in shaping neuronal synaptic development and plasticity.

neuroscience↗

bioRxiv2025

Photoperiod decoder 1 regulates seasonal changes in energy metabolism through the growth hormone signaling pathway

Seasonal changes in metabolism are crucial for animals to adapt to annual environmental fluctuations. However, the molecular mechanisms underlying these adaptations remain poorly understood. Here, we identified a novel gene, photoperiod decoder 1 (phod1), which exhibits a unique bimodal expression pattern under long-day conditions in Japanese medaka fish (Oryzias latipes). While phod1 is conserved across many vertebrates, except for eutherians, its function remained unknown. Single-cell RNA sequencing analysis revealed that phod1 is predominantly expressed in specific pituitary cells that co-express opsin and circadian clock genes. Transcriptomic analysis using phod1 knockout fish demonstrated that phod1 is essential for photoperiodic regulation of growth hormone. Furthermore, transcriptomic and metabolomic analyses of the liver, the primary target of growth hormone, revealed significant alterations in energy metabolism. Behavioral analysis also showed that phod1 knockout fish exhibited significantly reduced locomotor activity. These findings indicate that phod1 plays a crucial role in seasonal metabolic adaptation through modulation of the growth hormone signaling pathway.

physiology↗

bioRxiv2025

Drastic genome reduction driven by parasitic lifestyle: Two complete genomes of endosymbiotic bacteria possibly hosted by a dinoflagellate

Bacteria with endosymbiotic lifestyles often exhibit dramatic genome reduction. While the reduction of genomes in intracellular symbionts of animals, including parasitic bacteria, has been extensively studied, less is known about such bacteria associated with single-celled eukaryotes. Here, we report the genomes of two novel gammaproteobacterial lineages, RS3 and XS4, identified as putative parasitic endosymbionts of the dinoflagellate Citharistes regius. Phylogenetic analyses suggest that RS3 and XS4 belong to the family Fastidiosibacteraceae within the order Beggiatoales, forming independent lineages therein. The genomes of RS3 and XS4 are 529 Kbp and 436 Kbp in size, respectively, revealing drastic genome reduction compared to related bacterial genomes. XS4, which has a particularly reduced genome with low GC content, uses an alternative genetic code, in which UGA assigned tryptophan. The small genomes of RS3 and XS4 encode a limited number of proteins, retaining only approximately 20% of the predicted ancestral proteome. Metabolic reconstruction suggests that RS3 and XS4 are energy parasites, heavily dependent on their host for essential metabolites. Furthermore, we found that the ancestor of both genomes likely acquired an ADP:ATP antiporter gene via horizontal gene transfer, an event that may have enabled their evolution as energy parasites by facilitating the acquisition of ATP from their host. These observations on novel bacteria with highly reduced genomes expand our understanding of the phylogenetic and genomic diversity of endosymbiotic bacteria in protists.

evolutionary biology↗

bioRxiv2024

Gene therapy for targeting a prenatally enriched potassium channel associated with severe childhood epilepsy and premature death

Dysfunction of the sodium-activated potassium channel KNa1.1 (encoded by KCNT1) is associated with a severe condition characterized by frequent seizures (up to hundreds per day) and is often fatal by age three years. We defined the early developmental onset of KNa1.1 channels in prenatal and neonatal brain tissue, establishing a timeline for pathophysiology and a window for therapeutic intervention. Using patch-clamp electrophysiology, we observed age-dependent increases in KNa1.1 K+conductance. In neurons derived from a child with a gain-of-function KCNT1 pathogenic variant (p.R474H), we detected abnormal excitability and action potential afterhyperpolarization kinetics. In a clinical trial, two individuals with the p.R474H variant showed dramatic reductions in seizure occurrence and severity with a first-in-human antisense oligonucleotide (ASO) RNA therapy. ASO-treated p.R474H neurons in vitro exhibited normalized spiking and burst properties. Finally, we demonstrated the feasibility of ASO knockdown of KNa1.1 in midgestation human neurons, suggesting potential for early therapeutic intervention before the onset of epileptic encephalopathy. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/620125v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@eaf38corg.highwire.dtl.DTLVardef@11b7e3corg.highwire.dtl.DTLVardef@1fcce20org.highwire.dtl.DTLVardef@40d364_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

C-C chemokine receptor 4 deficiency exacerbates early atherosclerosis in mice

Chronic inflammation via dysregulation of T cell immune responses is critically involved in the pathogenesis of atherosclerotic cardiovascular disease. Improving the balance between proinflammatory T cells and anti-inflammatory regulatory T cells (Tregs) may be an attractive approach for treating atherosclerosis. Although C-C chemokine receptor 4 (CCR4) has been shown to mediate the recruitment of T cells to inflamed tissues, its role in atherosclerosis is unclear. Here, we show that genetic deletion of CCR4 in hypercholesterolemic mice accelerates the development of early atherosclerotic lesions characterized by an inflammatory plaque phenotype. This was associated with the augmentation of proinflammatory T helper type 1 (Th1) cell responses in peripheral lymphoid tissues, para-aortic lymph nodes, and atherosclerotic aorta. Mechanistically, CCR4 deficiency in Tregs impaired their suppressive function and tended to inhibit their migration to the atherosclerotic aorta, and subsequently augmented Th1 cell-mediated immune responses through defective regulation of dendritic cell function, which accelerated aortic inflammation and atherosclerotic lesion development. Thus, we revealed a previously unrecognized role for CCR4 in controlling the early stage of atherosclerosis via Treg-dependent regulation of proinflammatory T cell responses. Our data suggest that CCR4 is an important negative regulator of atherosclerosis.

immunology↗

bioRxiv2024

Convergent reductive evolution of cyanobacteria in symbiosis with Dinophysiales dinoflagellates

The diversity of marine cyanobacteria has been extensively studied due to their vital roles in ocean primary production. However, little is understood about the diversity of cyanobacterial species involved in symbiotic relationships. In this study, we successfully sequenced the complete genome of a cyanobacterium in symbiosis with Citharistes regius, a dinoflagellate species thriving in the open ocean. A phylogenomic analysis revealed that the cyanobacterium (CregCyn) belongs to the marine picocyanobacterial lineage, akin to another cyanobacterial symbiont (OmCyn) of a different dinoflagellate closely related to Citharistes. Nevertheless, these two symbionts are distinct lineages, suggesting independent origins of their symbiotic lifestyles. Despite the distinct origins, the genome analyses of CregCyn revealed shared characteristics with OmCyn, including an obligate symbiotic relationship with the host dinoflagellates and a degree of genome reduction. In contrast, a detailed analysis of genome subregions unveiled that the CregCyn genome carries genomic islands that are not found in the OmCyn genome. The presence of the genomic islands implies that exogenous genes have been integrated into the CregCyn genome at some point in its evolution. This study contributes to our understanding of the complex history of the symbiosis between dinoflagellates and cyanobacteria, as well as the genomic diversity of marine picocyanobacteria.

evolutionary biology↗

bioRxiv2024

CAP peptide artificially induces insect gall

Galls caused by gall-inducing insects in their host plants clearly illustrate the concept of extended phenotype, which refers to traits expressed in a host organism when manipulated by a parasite. Candidate effector molecules involved in gall formation, such as phytohormones, amino acids, and proteins, have been reported in numerous studies. However, to date, no attempts to artificially regenerate gall structures using effector candidates have been reported. In this study, we tested the peptide from Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins, CAP peptide as a gall-inducing effector candidate obtained from transcripts isolated from the horned gall aphid, (Schlechtendalia chinensis) through in silico screening and the Arabidopsis-based gall-forming assay, which is a bioassay system for analysing the molecular mechanisms of gall formation. Furthermore, we succeeded in generating an artificial gall in the host plant Veronica peregrina, without any insect parasitism, using three minimal effector elements: CAP peptide, auxin, and cytokinin. Given the strong similarities observed in organ structure with a central cavity and three types of tissue and gene expression patterns between the native and artificial galls, we concluded that CAP peptide is a general gall-inducing effector peptide secreted by gall-inducing insects.

molecular biology↗

bioRxiv2023

Epigenetic heterogeneity of the Notch signaling components in the human developing retina

ObjectiveThe regulation of receptor expression is crucial for fine-tuned signal transduction. Notch signaling is a key signaling pathway involved in retinal development. Although the involvement of this signaling pathway in the differentiation of retinal ganglion cells has been documented, less is known about its involvement in earlier stages of retinal progenitor cell differentiation. To clarify the timing of Notch receptor expression in undifferentiated retinal progenitor cells and elucidate the possible involvement of chromatin remodeling in the regulation of Notch receptor expressions, we re-analyzed publicly available human fetal retina single-cell RNA-seq and ATAC-seq data. ResultsOn days 59, 74, and 78, we observed NOTCH1 mRNA expression in early retinal progenitor cells, which diminished at later stages of differentiation. Integration of single-cell RNA-seq and ATAC-seq revealed that chromatin remodeling in part of the NOTCH1 locus was accompanied by transitions in its mRNA expression. Importantly, chromatin accessibility in the region upstream of NOTCH1 depended on the differentiated cell types. These results suggest that chromatin remodeling may be involved in the differential expression of NOTCH1, although another type of Notch mRNA expression regulation may exist.

developmental biology↗

bioRxiv2023

Immune-Epithelial Dynamics and Tissue Remodeling in Chronically Inflamed Nasal Epithelium via Multi-scaled Transcriptomics

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity that affects millions of individuals worldwide. The complex pathophysiology of CRS remains poorly understood, with emerging evidence implicating the orchestration between diverse immune and epithelial cell types in disease progression. We applied single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to both dissociated and intact, freshly isolated sinonasal human tissues to investigate the cellular and molecular heterogeneity of CRS with and without nasal polyp formation compared to non-CRS control samples. Our findings reveal a mechanism for macrophage-eosinophil recruitment into the nasal mucosa, systematic dysregulation of CD4+ and CD8+ T cells, and enrichment of mast cell populations to the upper airway tissues with intricate interactions between mast cells and CD4 T cells. Additionally, we identify immune-epithelial interactions and dysregulation, particularly involving understudied basal progenitor cells and Tuft chemosensory cells. We further describe a distinct basal cell differential trajectory in CRS patients with nasal polyps (NP), and link it to NP formation through immune-epithelial remodeling. By harnessing stringent patient tissue selection and advanced technologies, our study unveils novel aspects of CRS pathophysiology, and sheds light onto both intricate immune and epithelial cell interactions within the disrupted CRS tissue microenvironment and promising targets for therapeutic intervention. These findings expand upon existing knowledge of nasal inflammation and provide a comprehensive resource towards understanding the cellular and molecular mechanisms underlying this uniquely complex disease entity, and beyond.

immunology↗