Biology subjects

Cui, C.

Publications and source records attributed to Cui, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Glioblastoma Invasion Remodels Neural Circuits and Drives Persistent GABAergic Dysfunction in Human Brain Organoids

BackgroundGlioblastoma (GBM) is characterized by neurological dysfunction caused by tumor cells that interact with and alter neuronal circuits. However, the specific neuronal populations and molecular mechanisms most susceptible to GBM invasion remain poorly understood. MethodsWe created a human tumor-brain organoid model by combining U87 glioblastoma cells with iPSC-derived neural organoids. This system enabled us to study tumor-neural interactions over an extended period under standard temozolomide (TMZ) treatment. We used single-cell transcriptomics to monitor cell-type-specific responses. ResultsOur model recapitulated the diffuse infiltration observed in patients, leading to extensive structural remodeling and a profound loss of neuronal and glial populations. Single-cell analysis revealed that TMZ suppressed proliferative and biosynthetic programs but enriched for stress-responsive, mesenchymal-like, and therapy-adapted tumor states. Notably, GABAergic neurons exhibited the greatest transcriptional vulnerability, with [~]36% (7,499 of 20,659) of genes differentially expressed. Invasion triggered endoplasmic reticulum stress and shut down metabolic, respiratory, synaptic, and ion-homeostatic pathways. Crucially, SLC12A5-expressing GABAergic neurons plummeted from 31% to 12%, accompanied by a sharp decline in KCC2 protein expression. While TMZ partially rescued neuronal metabolic and electron transport chain function, it failed to restore SLC12A5/KCC2 expression or inhibitory signaling. ConclusionsGBM invasion leads to a continued imbalance of chloride in GABAergic networks, and this disruption remains even after undergoing tumor-targeted chemotherapy. This human iPSC-derived tumor-brain organoid platform provides a reliable and scalable system for studying complex tumor-neural interactions and exploring therapeutic approaches that aim to eliminate the tumor while preserving neural function.

cancer biology↗

bioRxiv2026

Older adults amplify passive gait stability during obstacle crossing without weakening the stabilizing synergy

Older adults sustain disproportionately severe injuries from trip-induced falls during obstacle crossing. Such falls depend partly on forward momentum when the foot crosses the obstacle. MOSAP, an index of passive dynamic gait stability, reflects this momentum. We quantified MOSAP and a synergy index from uncontrolled manifold analysis of step length and extrapolated center of mass in 25 young (21.6 {+/-} 3.5 yr) and 23 older adults (68 {+/-} 4.3 yr) during unobstructed and obstructed walking, to test whether MOSAP increases during obstacle crossing and whether it is actively stabilized at each step. Both groups increased MOSAP progressively over two approach steps by reducing forward momentum and shifting the center of mass posteriorly. Older adults showed greater increases at the crossing steps. The synergy index was positive for all steps, showing that deviations in step length and extrapolated center of mass covaried to stabilize MOSAP at step-specific values. The synergy index was not influenced by age. We conclude that adults actively recruit passive body mechanics while approaching and crossing obstacles to reduce the risk of a trip becoming a fall. Older adults amplify this strategy to compensate for diminished neuromuscular corrective capabilities.

physiology↗

bioRxiv2026

Exercise-induced sweat suppresses depression-like behaviors in mice

Depression represents a major global public health challenge. Current antidepressant therapies are often limited by significant side effects, delayed onset of action, and suboptimal efficacy, creating an urgent need for the development of novel interventions. In this study, using a transcriptome-based bioinformatics pipeline, we found that the gene signature of depression is significantly anti-correlated with that of exercise-induced sweat (EIS), suggesting that EIS may have the potential to treat depression. To validate this prediction, we first established a lipopolysaccharide-induced mouse model of depression and then evaluated the therapeutic effects of EIS in comparison with the positive control fluoxetine. Our results show that EIS treatment significantly suppresses depressive and anxiety-like behaviors, as evidenced by increased sucrose preference in the sucrose preference test, reduced immobility in the tail suspension test, and enhanced exploratory activity in the elevated plus maze. Notably, high-dose EIS intervention achieved therapeutic efficacy comparable to, or even better than, that of fluoxetine. This study identifies EIS as a novel bioactive intervention and an innovative strategy for treating depression, and opens a new avenue in sports medicine by investigating the potential beneficial effects of EIS.

neuroscience↗

bioRxiv2026

Landscape of reversion alterations in homologous recombination genes reveals evolutionary constraints

Reversion mutations (REVs) restore homologous recombination repair (HRR) and confer resistance to PARP inhibitors (PARPi) in HR-deficient cancers. Yet, their prevalence, mechanisms, and biological constraints remain undefined. We analyzed genomic profiling of 609,464 tissue and liquid biopsy samples across multiple cancer types to delineate the pan-cancer landscape of REVs. REVs were identified in eight HRR genes, most frequently BRCA2 and BRCA1 and notably never in ATM or CHEK2. REVs exclusively impacted truncating pathogenic variants, predominantly through large in-frame and exon-level deletions, associated with repetitive sequences. Conserved functional domains are relatively depleted of REVs. Structural modeling and functional studies support that exon-level deletions preserve critical domain architecture and confer PARPi resistance. The study establishes HRR reversion as a structurally permissive, yet evolutionarily constrained, resistance mechanism with implications on response, monitoring, and therapeutic strategy. One Sentence SummaryHomologous recombination reversion evolves through structurally tolerated, microhomology-driven alterations that restore DNA repair under therapeutic selection across cancers.

cancer biology↗

bioRxiv2026

Combination of engineered cell type-specific promoters and a high-efficiency AAV capsid restores hearing in adult DFNB1 mice model with demonstrated safety in nonhuman primate

A major challenge in gene therapy for GJB2-related hearing loss (DFNB1)--the most common form of hereditary deafness--is achieving efficient and precise connexin 26 delivery. Herein, we engineered two cell type-specific promoters (GJB2-1 and WFS1-2274) and developed an AAV capsid, AAV-MAS012, with enhanced transduction efficiency in mature cochlear cells. Our AAV-mediated gene therapy systems restored hearing of low-to-mid-frequencies in newborn Gjb2 cKO mice to wild-type levels and maintained for 45 weeks. Additionally, our therapeutic systems restored low-to-mid-frequencies hearing function to wild-type levels in adult Gjb2 cKO mice. A humanized version of the therapy, AAV-MAS012-WFS1-2274-hGJB2, rescued hearing function in two distinct Gjb2-deficient mouse models, and demonstrated a favorable safety profile in nonhuman primates. This study represents the first successful hearing restoration in adult Gjb2-deficient mice. The significant therapeutic efficacy of the humanized gene therapy system shows great potential for clinical translation in DFNB1 patients.

genetics↗

bioRxiv2026

Disease diagnosis via sperm motility variations induced by body fluids in bioassay

Precise diagnosis of high-risk conditions such as cardiovascular and cerebrovascular diseases still remains a challenge. We previously developed a microfluidic chip for sperm selection and observed that sperm motility is highly sensitive to environmental changes. Building on this finding, we hypothesized that motility traits of sperm could be differentially modulated by body fluids from healthy versus diseased individuals, thereby serving as potential biomarkers for disease diagnosis. To test this hypothesis, we designed a diagnostic system in which mouse sperm were co-incubated with serum samples from patients with myocardial infarction, cerebral infarction, and pancreatitis, along with matched healthy controls. Key kinematic parameters--including motility rate (MR), curvilinear velocity (VCL), straight-line velocity (VSL), linearity (LIN), and amplitude of lateral head displacement (ALH)--were analyzed using a multiparameter sperm quality analysis system. The results revealed that disease-specific serum induced distinct and reproducible changes in sperm motility patterns, enabling accurate discrimination between healthy and pathological conditions. Evaluation of these motility parameters demonstrated high diagnostic performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.719 to 0.888. This sperm-based bioassay offers a non-invasive, rapid, and cost-effective platform for disease detection and personalized health assessment, with the potential to complement existing diagnostic approaches.

bioengineering↗

bioRxiv2026

Identification of Novel Extracellular Vesicles Scaffold Proteins for Versatile Cargo Engineering

Extracellular vesicles (EVs) are promising drug delivery platforms that have been engineered to carry various drug modalities. Key strategies for generating those therapeutic EVs involve the direct fusion of protein of interest (POI) to EVs scaffold proteins with inherently high EVs-sorting ability. In this work, we identified raftlin (RFTN1) and poliovirus receptor (PVR) as novel EVs scaffold proteins for loading EVs lumen and surface cargos respectively. Truncation studies revealed that the N-terminus 15 residues from RFTN1 (RFTN1-N15) were sufficient for EVs engineering, as demonstrated by distinct cargos including gene editing tools, cytosolic enzymes as well as type II transmembrane proteins. On the other hand, PVR efficiently displayed secreted proteins including antibodies and serum albumins on EVs surface. Critically, RFTN1 and PVR-engineered EVs demonstrated consistent and efficient cargo delivery in vivo. In summary, the discovery of RFTN1 and PVR can potentially benefit EVs engineering for both fundamental research and clinical translation in the future.

bioengineering↗

bioRxiv2025

Tibetan near-complete pangenome reveals complex variants underlying high-altitude adaptation

Genomic diversity in indigenous populations offers critical insights into human evolution and population-specific adaptation. Here, we generated 70 near-complete, fully phased genome assemblies from 35 high-altitude Tibetan trios and identified 4.55 million small variants and 63,031 structural variants (SVs) absent from the current global pangenome reference. Comparative analyses with a 595 globally diverse long-read genome dataset revealed 207 previously uncharacterized Tibetan-enriched SVs spanning 275 genes implicated in high-altitude physiological adaptation. Genotyping these SVs in 1,164 Tibetan and Han individuals with 88 physiological traits reveals five variants significantly associated with cardiopulmonary and hematological phenotypes central to hypoxia adaptation. We further map 2.45 Gb of archaic hominin sequences in Tibetans and uncover 18 previously unrecognized introgressed regions enriched in Tibetans with genes related to hematopoiesis and lung function. These regions harbor five Tibetan-enriched SVs, indicating that archaic introgression contributed SVs relevant to human adaptation. Together, these findings reveal substantial uncharacterized genomic diversity in Tibetans and highlight a previously underappreciated role of SVs and archaic SVs in shaping human evolution and high-altitude adaptation.

genomics↗

bioRxiv2025

In form for a swarm: programmable neutrophil swarming impacts infection outcome

Many migrating cells pattern signalling molecules to support their accumulation in target tissues. During inflammation, neutrophils achieve rapid swarming at sites of injury or infection by generating spatiotemporal gradients of chemoattractants. Whether these self-generated behaviours can be re-programmed to change disease course is unclear. Here, we show that neutrophil chemoattractant patterning machinery is subject to transcriptional reprogramming after microbial experience, leading to enhanced swarming and control of infection at subsequent wound sites in zebrafish. Through in vitro assays, we demonstrate that "trained swarming phenotypes" are cell-intrinsic and independent of the nature of the microbial target. Furthermore, genetic enhancement of 5-lipoxygenase in neutrophils is sufficient to improve neutrophil swarming and resistance to wound infection. Through mathematical modelling, we demonstrate that neutrophil-intrinsic alterations in chemoattractant release are sufficient to recapitulate trained swarming in infection-experienced animals. Together, these data suggest new routes for reprogramming cell migration in disease settings, via manipulating their ability to shape chemoattractant landscapes.

immunology↗

bioRxiv2025

A large-scale foundation model for bulk transcriptomes

Large language models (LLMs) have emerged as powerful foundation models leading to breakthroughs in transcriptome analysis. However, current RNA-seq foundation models are exclusively pretrained on sparse single-cell RNA-seq (scRNA-seq) data, which typically detects only [~]3000 genes per cell. This thus creates a critical gap in models specifically designed for bulk transcriptomes, a fundamentally different modality capable of profiling [~]16,000 genes per sample. Here we propose BulkFormer, a large-scale foundation model for bulk transcriptome analysis. With 150 million parameters covering about 20,000 protein-coding genes, BulkFormer is pretrained on over 500,000 human bulk transcriptomic profiles. BulkFormer incorporates a hybrid encoder architecture, combining a graph neural network to capture explicit gene-gene interactions and a performer module to model global expression dependencies. As a result, despite incurring much lower training costs than scRNA-seq foundation models, BulkFormer consistently outperforms them in all six downstream tasks: transcriptome imputation, disease annotation, prognosis modeling, drug response prediction, compound perturbation simulation, and gene essentiality scoring. Notably, BulkFormer not only enhances the discovery of novel clinical biomarkers but also uncovers latent disease mechanisms by imputing biologically meaningful gene expression. Collectively, these results demonstrate BulkFormers power as a versatile and robust framework for bulk transcriptome modeling and biomedical discovery, bridging a critical gap in the current foundation model landscape.

bioinformatics↗

bioRxiv2025

Mechanisms of KCNQ1 gating modulation by KCNE1/3 for cell-specific function

KCNQ1 potassium channels are essential for physiological processes such as cardiac rhythm and intestinal chloride secretion. KCNE-family subunits (KCNE1-5) associate with KCNQ1, conferring distinct properties across various tissues. KCNQ1 activation requires membrane depolarization and phosphatidylinositol 4,5-bisphosphate (PIP2) whose cellular levels are controlled by Gq-coupled GPCR activation. While modulation of KCNQ1s voltage-dependent activation by KCNE1/3 is well-characterized, their effects on PIP2-dependent gating of KCNQ1 via GPCR signaling remain less understood. Here we resolved structures of KCNQ1-KCNE1 and reassessed reported KCNQ1-KCNE3 structures with and without PIP2. We revealed that KCNQ1-KCNE1/3 complexes feature two PIP2-binding sites, with KCNE1/3 contributing to a previously overlooked, uncharacterized site involving residues critical for voltage sensor and pore domain coupling. Via this site, KCNE1 and KCNE3 distinctly modulate the PIP2-dependent gating, in addition to the voltage sensitivity, of KCNQ1. Consequently, KCNE3 converts KCNQ1 into a voltage-insensitive PIP2-gated channel governed by GPCR signaling to maintain ion homeostasis in non-excitable cells. KCNE1, by significantly enhancing KCNQ1s PIP2 affinity and resistance to GPCR regulation, forms predominantly voltage-gated channels with KCNQ1 for conducting the slow-delayed rectifier current in excitable cardiac cells. Our study highlights how KCNE1/3 modulates KCNQ1 gating in different cellular contexts, providing insights for tissue-specifically targeting multi-functional channels.

biochemistry↗

bioRxiv2025

High-throughput protein target mapping enables accelerated bioactivity discovery for ToxCast and PFAS compounds

Chemical pollution is a global threat to human health, yet the toxicity mechanism of most contaminants remains unknown. Here, we applied an ultrahigh-throughput affinity-selection mass spectrometry (AS-MS) platform to systematically identify protein targets of prioritized chemical contaminants. After benchmarking the platform, we screened 50 human proteins against 481 prioritized chemicals, including 446 ToxCast chemicals and 35 per-and polyfluoroalkyl substances (PFAS). Among 24,050 interactions assessed, we discovered 35 novel interactions involving 14 proteins, with fatty acid-binding proteins (FABPs) emerging as the most ligandable protein family. Given this, we selected FABPs for further validation, which revealed a distinct PFAS binding pattern: legacy PFAS selectively bound to FABP1, whereas replacement compounds, PFECAs, unexpectedly interacted with all FABPs. X-ray crystallography further revealed that the ether group enhances molecular flexibility of alternative PFAS, to accommodate the binding pockets of FABPs. Our findings demonstrate that AS-MS is a robust platform for the discovery of novel protein targets beyond the scope of the ToxCast program and highlight the broader protein-binding spectrum of alternative PFAS as potential regrettable substitutes.

pharmacology and toxicology↗

bioRxiv2025

Detection of Diffuse to Focal Myocardial Fibrosis by Cardiovascular Magnetic Resonance Against Histology in Mini-Swine

BackgroundMyocardial fibrosis predicts adverse outcomes in myocardial infarction (MI) and other cardiovascular conditions. Cardiovascular magnetic resonance (CMR) can non-invasively detect focal and diffuse myocardial fibrosis, but comprehensive validation against histology remains scarce. AimsTo assess the comparative diagnostic performance of CMR methods in detecting myocardial fibrosis, using a mini-swine model and histology as gold standard. MethodsEighteen mini-swine (16 MI; 2 healthy) underwent CMR cine, LGE, T1- and ECV-mapping. Two commonly-used T1-mapping methods - MOLLI 5(3)3 and ShMOLLI 5(1)1(1)1 - were included. Pathological sections were categorized as infarcted, peri-infarct, remote and healthy myocardium based on triphenyl tetrazolium chloride staining. Fibrotic burden was quantified by collagen volume fraction (CVF) into severe (CVF[≥]30%), moderate (CVF=10-25%), and mild (CVF=3-14%). The relationships between LGE, T1, ECV and CVF, and diagnostic performance using area-under-the-curve (AUC), were analyzed. ResultsFor detecting severe fibrosis, LGE, T1 and ECV all had excellent diagnostic performance (AUC: LGE=0.93, ECVShMOLLI=0.96, T1ShMOLLI=0.91, T1MOLLI=0.93, ECVMOLLI=0.88). ECVShMOLLI showed significantly better discriminatory accuracy than ECVMOLLI in detecting severe fibrosis and MI (both p<0.05), with the highest correlation to CVF (ECVShMOLLI r=0.86, ECVMOLLI r=0.82, T1ShMOLLI r=0.77, T1MOLLI r=0.77, semi-quantitative LGE r=0.75). Only T1ShMOLLI and ECVShMOLLI, but not LGE or T1MOLLI/ECVMOLLI, differentiated remote myocardium with mild fibrosis (CVF=8.23%) from healthy myocardium (CVF=2.01%). ConclusionsCMR can detect severe to mild myocardial fibrosis as validated against histology. For low-grade fibrosis, T1-mapping significantly outperformed LGE. Choice of CMR methodologies matters for myocardial fibrosis detection, which has importance for clinical trial design.

pathology↗

bioRxiv2024

SpaMTP: Integrative Statistical Analysis and Visualisation of Spatial Metabolomics and Transcriptomics data.

The ability to spatially measure multi-modal data provides an unprecedented opportunity to comprehensively explore molecular regulation at transcriptional, translational and metabolic levels to acquire insights on cellular activities underpinning health and disease. However, there is currently a lack of analytical tools to integrate complementary information across different spatial-omics data modalities, particularly with respect to spatial metabolomics data, which is becoming increasingly invaluable. We introduce SpaMTP, a versatile software that implements an end-to-end integrative analysis of spatial metabolomics and transcriptomics data. Based in R, SpaMTP bridges processing functionalities for metabolomics data from Cardinal with user-friendly cell-centric analyses implemented in Seurat. Furthermore, SpaMTPs comprehensive analysis pipeline covers (1) automated mass-to-charge ratio (m/z) metabolite annotation; (2) a wide range of metabolite-gene based downstream statistical analyses including differential expression, pathway analysis, and correlation analysis; (3) integrative spatial-omics analysis; and (4) a suite of visualisation functions. For flexibility and interoperability, SpaMTP includes various functions for data import/export and object conversion, enabling seamless integration with other R and Python packages. We demonstrated the utility of SpaMTP to draw new biological understandings through analysing two biological system. We believe this software and implemented methods will be broadly utilised in spatial multi-omics and spatial metabolomics analyses.

bioinformatics↗

bioRxiv2024

Soluble guanylyl cyclase, the NO-receptor, regulates endothelium-dependent vascular relaxation via its transnitrosation activity.

We previously demonstrated that the NO-receptor soluble guanylyl cyclase (GC1) has the ability to transnitrosate other proteins in a reaction that involves, in some cases, oxidized Thioredoxin 1 (oTrx1). This transnitrosation cascade was established in vitro and we identified by mass spectrometry and mutational analysis Cys 610 (C610) of GC1 -subunit as a major donor of S-nitrosothiols (SNO). To assay the relevance of GC1 transnitrosation under physiological conditions and in oxidative pathologies, we studied a knock-in mouse in which C610 was replaced with a serine (KI C610S) under basal or angiotensin II (Ang II)-treated conditions. Despite similar GC1 expression and NO-stimulated cGMP-forming activity, the Ang II-treated KI mice displayed exacerbated oxidative pathologies including higher mean arterial pressure and more severe cardiac dysfunctions compared to the Ang II-treated WT. These phenotypes were associated with a drastic decrease in global S-nitrosation and in levels of SNO-Trx1 and SNO-RhoA in the KI mice. To investigate the mechanism underlying the dysregulation of blood pressure despite an intact NO-cGMP axis, pressure myography and in vivo intravital microscopy were conducted to analyze the vascular resistance tone. Both approaches indicated that, even in the absence of oxidative stress, the single mutation C610S led to a significant deficiency in acetylcholine-induced vasorelaxation while smooth muscle relaxation in response to NO remained unchanged. These findings indicate that the C610S mutation uncoupled the two NO signaling pathways involved in the endothelium and smooth muscle vasorelaxation and suggest that GC1-dependent S-nitrosation is a key player in endothelium-derived hyperpolarization.

biochemistry↗

bioRxiv2024

2.6-A resolution cryo-EM structure of a class Ia ribonucleotide reductase trapped with mechanism-based inhibitor N3CDP

Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides using radical-based chemistry. For class Ia RNRs, the radical species is stored in a separate subunit ({beta}2) from the subunit housing the active site (2), requiring the formation of a short-lived 2{beta}2 complex and long-range radical transfer (RT). RT occurs via proton-coupled electron transfer (PCET) over a long distance (~32-[A]) and involves the formation and decay of multiple amino acid radical species. Here, we use cryogenic-electron microscopy and a mechanism-based inhibitor 2'-azido-2'-deoxycytidine-5'-diphosphate (N3CDP) to trap a wild-type 2{beta}2 complex of E. coli class Ia RNR. We find that one subunit has turned over and that the other is trapped, bound to {beta} in a mid-turnover state. Instead of N3CDP in the active site, forward RT has resulted in N2 loss, migration of the third nitrogen from the ribose C2' to C3' positions, and attachment of this nitrogen to the sulfur of cysteine-225. To the best of our knowledge, this is the first time an inhibitor has been visualized as an adduct to an RNR. Additionally, this structure reveals the positions of PCET residues following forward RT, complementing the previous structure that depicted a pre-turnover PCET pathway and suggesting how PCET is gated at the -{beta} interface. This N3CDP-trapped structure is also of sufficient resolution (2.6 [A]) to visualize water molecules, allowing us to evaluate the proposal that water molecules are proton acceptors and donors as part of the PCET process. Significance StatementSeveral FDA-approved cancer drugs target human ribonucleotide reductase (RNR), a radical enzyme that produces the requisite deoxyribonucleotides for DNA biosynthesis and repair. Human RNR is a class Ia enzyme that requires radical transfer (RT) from a {beta}2 subunit to an 2 subunit on every round of turnover. Long-range RT is both a remarkable feature and an Achilles heel, given that inhibitors can intercept the radical species. Here we present a cryogenic electron microscopy (cryo-EM) structure of the best studied class Ia RNR, the enzyme from E. coli, in which 2 and {beta}2 subunits have been trapped together using a mechanism-based inhibitor. This structure provides insight into both the mechanism of RNR inhibition and the mechanism of long-range RT.

biophysics↗

bioRxiv2024

Mesenchymal stem cell-derived extracellular vesicles alleviate imiquimod-induced psoriasis symptoms in a mouse disease model

Psoriasis is an immune mediated, chronic inflammatory skin disease. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have inherent immunomodulatory potency from their parental cells, the mesenchymal stem cells (MSCs). In this study, we revealed the application potential of MSC-EVs to alleviate psoriatic symptoms in imiquimod-induced psoriasis mouse model.

physiology↗

bioRxiv2024

IL-4 Licenses B Cell Activation Through Cholesterol Synthesis

Lymphocyte activation involves a transition from quiescence and associated catabolic metabolism to a metabolic state with noted similarities to cancer cells such as heavy reliance on aerobic glycolysis for energy demands and increased nutrient requirements for biomass accumulation and cell division1-3. Following antigen receptor ligation, lymphocytes require spatiotemporally distinct "second signals". These include costimulatory receptor or cytokine signaling, which engage discrete programs that often involve remodeling of organelles and increased nutrient uptake or synthesis to meet changing biochemical demands4-6. One such signaling molecule, IL-4, is a highly pleiotropic cytokine that was first identified as a B cell co-mitogen over 30 years ago7. However, how IL-4 signaling mechanistically supports B cell proliferation is incompletely understood. Here, using single cell RNA sequencing we find that the cholesterol biosynthetic program is transcriptionally upregulated following IL-4 signaling during the early B cell response to influenza virus infection, and is required for B cell activation in vivo. By limiting lipid availability in vitro, we determine cholesterol to be essential for B cells to expand their endoplasmic reticulum, progress through cell cycle, and proliferate. In sum, we demonstrate that the well-known ability of IL-4 to act as a B cell growth factor is through a previously unknown rewiring of specific lipid anabolic programs, relieving sensitivity of cells to environmental nutrient availability.

immunology↗