Biology subjects

Jiang, Y.

Publications and source records attributed to Jiang, Y..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Synthetic Immunological Niche Reveals Early Immune Dysregulationand Stratifies Therapeutic Response in Type 1 Diabetes

In Type 1 Diabetes (T1D), disease onset and response to immunotherapy vary widely among individuals, reflecting heterogeneous stage-specific immune dysregulation that remains undefined. To investigate this heterogeneity, we engineered a microporous polycaprolactone scaffold that forms a synthetic immunological niche (IN) upon subcutaneous implantation, enabling in vivo capture of systemic immune dysregulation. In non-obese diabetic (NOD) mice, longitudinal transcriptomic profiling of IN-infiltrating cells identified early-stage genes relatively enriched for myeloid cells, followed by progressive increases in T cell-associated dysregulation at later stages that distinguished T1D progressors from non-progressors. We derived an early-stage IN-based T1D gene signature capturing immune alterations. The signature stratified NOD progressors from non-progressors as early as 6 weeks of age and was conserved across human T1D datasets, distinguishing T1D from non-diabetic individuals in spleen and pancreatic lymph node samples, but not peripheral blood. Signature-based stratification further revealed enrichment of macrophage-associated TNF- pathways in NOD progressors, validated in human T1D islets. Given heterogeneous response to anti-TNF- therapy, IN profiling identified resistance-associated mechanisms and enabled derivation of a pathway score that prospectively distinguished treatment-sensitive from resistant mice prior to therapy, establishing the IN as a minimally invasive platform for detecting stage-wise immune dysregulation and stratifying immunotherapy response in T1D.

bioengineering↗

bioRxiv2026

Molecular Glue-Induced Homodimerization Drives Targeted CRBN Autodegradation

Molecular glue degraders (MGDs) offer a sophisticated, proximity-based approach to protein modulation. In this study, we introduce LJY-3-60, a novel proximity-inducing agent that unexpectedly triggers the potent and selective autodegradation of CRBN. Evidence from CRISPR-Cas9 screening and IP-MS reveals that this degradation process is strictly governed by the intrinsic CRL4CRBN machinery, independent of any extrinsic E3 recruitment. Through a combination of cellular and biophysical characterizations, we demonstrate that LJY-3-60 acts as a molecular bridge to template CRBN homodimerization. This mechanism is unequivocally elucidated by the atomic-resolution co-crystal structure of the CRBNMidi-LJY-3-60 complex. The structure explicitly delineates the homodimerization interface, revealing how the ligand reorganizes the protein surface to stabilize a non-canonical architecture that drives trans-autoubiquitination and subsequent proteasomal degradation. Furthermore, LJY-3-60 serves as a highly effective, controllable off-switch to mitigate PROTAC-induced toxicity. Ultimately, this work delivers a robust chemical tool for modulating CRBN stability. By demonstrating how a small molecule can functionally mimic an endogenous E3 substrates degron to catalyse targeted autodegradation, this study establishes a rational structural framework for designing the next generation of self-destructive modulators in targeted protein degradation (TPD) therapeutics.

biochemistry↗

bioRxiv2026

Genome-wide maps of transcription factor footprints identify noncoding variants rewiring gene regulatory networks with varTFBridge

Genome-wide association studies have identified millions of noncoding loci linked to human traits, yet how these variants alter gene regulation remains a major challenge, particularly for rare variants where whole-genome sequencing cohorts and high-resolution functional annotations remain limited. Here we show that single-molecule deaminase footprinting (FOODIE) in K562 cells captures up to 103-fold heritability enrichment for erythroid traits despite covering 0.12% of the genome. We introduce varTFBridge, integrating FOODIE footprinting with AlphaGenome variant effect prediction to identify causal noncoding variants altering transcription factor (TF)-mediated regulation. Applied to 490,640 UK Biobank genomes across 13 erythrocyte traits, varTFBridge prioritises 113 high-confidence regulatory variants (104 common, 9 rare), encompassing 2,173 linkages along the variant-TF binding- gene-trait cascade across 64 TFs and 108 genes. varTFBridge recapitulates rs112233623 and resolves its mechanism: GATA1/TAL1 co-binding disruption at a CCND3 enhancer altering red blood cell count and volume.

bioinformatics↗

bioRxiv2026

Transformation and recombination of neural information in a brain network

Mammalian brain function relies on integrated interactions among interconnected neural structures. The principles by which regional activity is transformed into projection-specific signals and then recombined at targets elsewhere in the brain are fundamental to brain processing, but remain poorly understood. Here we study these phenomena using a genetically encoded probe that provides neurophysiological readouts from virally labeled projections on a brain-wide scale via functional magnetic resonance imaging (fMRI). By analyzing outputs from thalamic and cortical somatosensory processing regions in rats, we find that projection-specific neural population activity undergoes shifts in tuning and temporal characteristics as it emanates from source regions. Patterns of neural information flow to targeted brain structures reconfigure under different conditions of stimulation and rest, contrasting with intrinsic fMRI functional connectivity profiles, which remain constant. Excitatory and inhibitory projections are coactivated during stimulation, but their relative response amplitudes change dynamically between stimulus conditions and across repeated stimuli, suggesting mechanistic roles for network-wide shifts in excitation/inhibition balance. Our results thus reveal how information flow throughout a neural system reshapes to promote stimulus selectivity and provide underpinnings of large-scale brain phenomena.

neuroscience↗

bioRxiv2026

Large-scale simulations reveal evolutionary constraints on intrinsically disordered regions imposed by full-length protein architecture

Intrinsically disordered regions (IDRs) are pervasive in eukaryotic proteomes and play central roles in regulatory complexity and evolutionary innovation. While their conformational ensembles have been extensively characterized in isolation, most long IDRs function within multidomain proteins, where domain architecture may impose structural and evolutionary constraints. Here, we perform proteome-scale molecular dynamics simulations of 14,283 human proteins containing IDRs, integrating the Calvados coarse-grained force field with an elastic network representation of structured domains to model full-length architectures. Focusing on 8,988 long IDRs ([≥]100 residues), we systematically compare conformational properties in isolated versus full-length contexts. We find that 2,733 IDRs (over 30%) undergo significant conformational shifts when embedded within their native protein architecture, revealing pervasive structural coupling between ordered and disordered regions. Notably, IDRs positioned centrally within proteins are evolutionarily biased toward compact and rigid conformations, whereas those with strong charge clustering preferentially adopt extended and flexible states in full-length contexts. Functional enrichment analyses further demonstrate that compact-rigid IDRs are overrepresented in DNA-binding proteins, while extended-flexible IDRs are enriched in RNA-binding functions, suggesting coordinated structural-functional specialization. Together, these findings support a model in which long IDRs do not evolve as independent polymeric segments, but instead co-evolve with structured domains as integrated architectural modules. Our results provide quantitative evidence that full-length protein organization imposes systematic conformational constraints on IDRs, revealing a previously underappreciated dimension of protein structural evolution and offering a new framework for understanding domain-disorder co-evolution across complex proteomes.

biophysics↗

bioRxiv2026

Unique mineralization pattern revealed in TBCK syndrome mouse model

TBCK syndrome is a severe degenerative leukoencephalopathy with multisystem involvement. Neurodevelopmental, craniofacial, and pulmonary challenges are among the topmost effects on these children. TBCK has been implicated in endo-lysosomal regulation, RNA transport, and mTOR-associated pathways, all of which are critical for the development of mineralized tissue. Although craniofacial abnormalities can be clinically apparent, conventional imaging approaches may overlook subtle defects in mineral quality. Here, we apply our multimodal framework to investigate the mineralization of enamel, dentin, and alveolar bone in a Tbck knockout mouse model. This is the first time our multimodal framework will be applied to a genetic condition. Using micro-computed tomography (microCT), histology, nanoindentation, energy-dispersive spectroscopy, and Raman spectroscopy, we identify tissue- and stage-dependent mineral effects undetected by microCT alone. Tbck loss resulted in differences in enamel and dentin element compositions as early as secretory and transition stages, while mechanical properties remained undetected until maturation stage. Notably, Tbck knockout enamel exhibited reduced calcium and phosphorus content, along with increased carbon content during early mineralization, consistent with the retained organic matrix. Additionally, marked and opposing alterations in magnesium and iron levels began at the secretory stage. Together, these findings define a previously unrecognized mineralization signature associated with TBCK deficiency and establish multimodal hard-tissue analysis as a sensitive approach for detecting early craniofacial phenotypes in rare genetic disorders.

developmental biology↗

bioRxiv2026

Circumventing the synthesizability problem in generative molecular design

Generative structure-based drug design (SBDD) models have shown great promise to accelerate our ability to discover novel drug candidates. However, these models have been criticized for producing compounds that are not very synthesizable, and therefore not practically applicable to drug design. In this work, we propose a way to circumvent the synthesizability issue by introducing a model-guided virtual screening (MGVS) pipeline which pairs SBDD models with efficient chemical similarity search methods to identify synthesizable analogs of generated compounds in existing ultra-large compound databases. Using this approach, we demonstrate that synthesizable analogs of generated compounds with equivalent or better docking scores and similar predicted binding poses can be reliably identified across a wide range of protein targets. We find that MGVS outperforms standard virtual ligand screening (VLS), consistently yielding at least a 25x improvement in screening efficiency across three different SBDD models. As drug-like chemical spaces continue to grow and standard VLS methods focused on exhaustive screening become increasingly impractical, approaches like MGVS that effectively narrow the search space will become critical for advancing drug discovery.

bioinformatics↗

bioRxiv2026

Anti-IL1RAP Antibodies for Pan-Inhibition of IL-1 Family Cytokine Signaling in Inflammatory Diseases and Oncology

The interleukin-1 (IL-1) superfamily of cytokines--comprising the IL-1, IL-33, and IL-36 subfamilies--orchestrates a vast array of innate and adaptive immune responses. While physiological activation of these pathways is essential for host defense and tissue repair, their chronic dysregulation is pathognomonic of a broad spectrum of autoimmune diseases and malignancies. Current therapeutic modalities largely rely on the neutralization of single cytokines, an approach often limited by the functional redundancy and compensatory signaling loops inherent to the IL-1 superfamily. The Interleukin-1 Receptor Accessory Protein (IL1RAP) serves as an obligatory co-receptor for IL-1, IL-33, and IL-36 subfamilies, functioning as a molecular bottleneck for pro-inflammatory signaling. Herein, we report the development and comprehensive characterization of two humanized monoclonal antibodies, DXP-006 and DXP-106, which target a unique epitope on domain 2 of IL1RAP. Cryo-electron microscopy studies at 3.55 [A] resolution reveal that these antibodies lock the critical c2d2 loop of IL1RAP, sterically occluding its recruitment to IL-1R1, ST2 and IL-36R binary complexes and potently blockade IL-1, IL33, and IL-36 signaling. DXP-006, engineered with a half-life-extended and effector-silenced Fc, exerts profound efficacy in murine models of psoriasis, superior to the clinical benchmark bimekizumab. Conversely, DXP-106, engineered with a defucosylated Fc to enhance antibody-dependent cellular cytotoxicity, exhibits potent antitumor activity in non-small cell lung cancer xenografts. These findings position DXP-006 and DXP-106 as ideal therapeutics for IL-1 family-driven autoimmunity and IL1RAP-positive cancers. One Sentence SummaryAnti-IL1RAP antibodies block multiple IL-1 family cytokines simultaneously, showing superior efficacy in inflammation and cancer models.

immunology↗

bioRxiv2026

Neural Activity Related Sodium (NARS) fMRI Resolves Millisecond Neuronal Dynamics in the Rodent Cortex

Brain-wide, noninvasive methods that directly resolve neuronal activity on millisecond timescales are still lacking in neuroimaging. Hemodynamic fMRI (1H-based) provides whole-brain maps of activity, yet its vascular origin creates spatial and temporal displacements from neuronal events that complicate interpretation, especially in disease conditions where neurovascular coupling is altered. Here, we developed an ultrafast 23Na fMRI platform at 14 T that combines a reshuffled k-t 3D gradient echo readout (TR/TE, 10ms/1ms) with an implantable RF coil and respiration-gated acquisition. This configuration provides the sampling rate and SNR needed to probe quadrupolar T2*-weighted single quantum sodium dynamics on the neuronal timescale. Across rats and mice, somatosensory forepaw stimulation produced a localized 23Na signal decrease of ~2-3% in the FP-S1, peaking ~10-30 ms post-stimulus. The activity pattern is well matched with conventional BOLD-fMRI maps acquired in the same animals. Trial-by-trial measurements during simultaneous iGluSnFR glutamate fiber photometry demonstrated that larger evoked glutamate transients coincided with larger NARS decreases, supporting a neuronal origin of the NARS contrast. We interpret the negative NARS response as a transient activity-dependent redistribution of sodium ions toward restricted, protein-rich microdomains, where more restricted rotational dynamics may accelerate T2*short decay and produce a 2-3% signal decrease without requiring large changes in bulk sodium concentration. Together, these results establish neural activity-related sodium (NARS) fMRI as a viable approach for direct, mesoscale neuronal mapping with MRI at millisecond resolution. Graphical AbstractA reshuffled k-t 3D gradient echo (GRE) readout with an implantable figure-8 RF coil and respiration-gated trials captures a ~2-3% negative 23Na response peaking 10-30 ms after forepaw stimulation in the FP-S1. NARS fMRI responses co-localize with BOLD-fMRI and scale with iGluSnFR glutamate transients, consistent with activity-dependent shifts toward short-T2* sodium microenvironments. Table of Contents (TOC) BlurbYu et al. introduce NARS-fMRI, an ultrafast 23Na method that resolves millisecond neuronal dynamics in rodent FP-S1. The negative sodium response (10-30 ms) co-localizes with BOLD and correlates with glutamate photometry, supporting a direct neuronal origin.

biophysics↗

bioRxiv2026

High spatial resolution 23Na-MRI for ischemic brain injury detection

High spatial resolution sodium (23Na) imaging of brain lesions remains challenging due to the intrinsically low signal-to-noise ratio (SNR) of 23Na-MRI compared with conventional proton (1H) MRI. In this study, we established a high-resolution 23Na-MRI platform based on 14 T preclinical scanner using a dual-tuned head-implanted RF coil. This configuration enables the acquisition of 1H-based T2-weighted anatomical and diffusion-weighted imaging (DWI), as well as 23Na-MRI, from the same animal. Brain-wide 23Na-MRI with 300x300 {micro}m2 in-plane resolution was performed within the first 4 hours after acute middle cerebral artery occlusion (MCAO) induced ischemic stroke induction. Hyperintense 23Na-MRI signals were observed in the ischemic brain regions, presenting a contrast-to-noise ratio (CNR) that exceeded that of T2-weighted images. Infarct regions can be well-identified in the elevated 23Na signal, which is spatially consistent with regions of reduced apparent diffusion coefficient (ADC) values, indicating water restriction in the ischemic core. This work established implanted double-tuned 1H/23Na RF coils as a powerful approach for high-resolution 23Na-MRI readout, facilitating the early detection of ischemic brain injury.

neuroscience↗

bioRxiv2026

Clonal morphology-guided combination therapies overcome heterogeneity-driven drug tolerance

Tumor heterogeneity plays a critical role in tumor relapse and the development of drug resistance. Current personalized strategies, based on genetic profiling or bulk tumor drug sensitivity testing, offer limited clinical value as they overlook clonal heterogeneity. Here, through establishing primary tumor cell cultures from multiple metastatic sites, we observed that tumor cells exhibit high morphological plasticity and readily form distinct clonal morphologies during monoclonal expansion. Moreover, these heterogeneous clones displayed distinct tumorigenic and histological traits in orthotopic models, which may imply their differing clinical relevance in tumor progression. We also found that clonal morphological heterogeneity was exhibited by both established cell lines and primary lines derived from chemically induced tumor models. Subsequently, we analyzed the drug sensitivity profiles of tumor clones and identified clone-specific sensitive drugs. Despite limited in vitro synergy in pairwise combinations, both in vitro and in vivo assays confirmed their potent, clone-selective inhibition, suggesting rational drug combinations can precisely target distinct clonal populations. Taken together, Collectively, our findings propose that a heterogeneity-informed drug selection paradigm, enabled by rapid clonal morphology analysis of patient-derived cells, can be used to prevent recurrence and overcome resistance. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/703021v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@1db607dorg.highwire.dtl.DTLVardef@19bbcd4org.highwire.dtl.DTLVardef@18a3355org.highwire.dtl.DTLVardef@304794_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LITumor cells develop distinct morphologies during clonal expansion. C_LIO_LIDistinct morphologies serve as simple markers of tumor heterogeneity. C_LIO_LIDistinct clonal morphology defines a unique drug-response profile. C_LIO_LIClone-selective drug combinations combat heterogeneity-driven resistance. C_LI

cancer biology↗

bioRxiv2026

How Visual Experience Shapes Face Processing: Divergent Representational Strategies Emerge from Specialized and Diverse Visual Diets in Artificial Neural Networks

Face perception in humans is supported by specialized neural mechanisms, yet the developmental origins of these mechanisms remain debated. We trained two artificial neural networks (ANNs) on identical orientation-classification tasks but with distinct visual diets: one exposed exclusively to adult faces (Face-ANN) and the other to diverse object categories (Object-ANN). Face-ANN acquired human-like face-processing signatures, including robust performance on Mooney faces, infant faces, and minimal three-dot patterns, and a reliance on low-frequency global structure. However, it failed to recognize face-like objects or most animal faces (except for monkeys), indicating limited overgeneralization. Object-ANN showed the opposite profile, excelling at face-like objects and animal faces but failing on abstract faces. These dissociations demonstrate that domain-specific visual experience alone can give rise to core properties of human face perception, while broad visual experience supports flexible generalization and face pareidolia. Our findings highlight how distinct visual diets shape representational strategies and offer a computational framework for probing the evolutionary origins of face-selective systems.

neuroscience↗

bioRxiv2026

Molecular mechanisms of mitochondrial Ca2+ exchanger NCLX

Mitochondrial Ca2+ homeostasis is maintained through coordinated influx and efflux processes, with NCLX long recognized as the primary Ca2+ extruder operating via Na+/Ca2+ exchange. Here, we report cryo-EM structures of rat NCLX in cytosolic-facing occluded and open states. The central transmembrane (TM) domain of NCLX comprises ten helices arranged in two inverted, structurally similar halves, with two -repeats forming a central ion-binding pocket. Peripheral TMs 1 and 6 are loosely associated with the core and likely mediate alternative access to this site. These structural features closely resemble those of NCXs, indicating a conserved ion exchange mechanism. While NCLX retains the canonical Ca2+-binding site, it lacks several key Na+-binding residues found in NCXs, suggesting broader ion selectivity. Consistently, cell-based Ca2+ uptake assays show that NCLX mediates Ca2+ exchange using Na+, K+, Li+, and potentially protons as counterions. Based on the structural symmetry of NCLX and its bidirectional exchange capability, we propose a matrix-facing model and an alternating-access mechanism in which TMs 1 and 6 undergo sliding motions to enable ion exchange between cytosolic and matrix sides, analogous to NCX. These findings provide a structural and mechanistic framework for understanding NCLX-mediated Ca2+ transport in mitochondria.

biophysics↗

bioRxiv2026

Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload

The small molecule Necrocide 1 (NC1) constitutively activates human TRPM4, triggering Na influx and leading to necrotic cell death, a process termed Necrosis by Sodium Overload (NECSO). NC1 activation is specific to human TRPM4 and does not affect most of the other mammalian TRPM4 orthologs. Here, we elucidate the molecular mechanism underlying NC1 activation and its species-specific selectivity for human TRPM4 using a combination of single-particle cryo-EM, electrophysiology, and cell death assays. We identify the NC1-binding site and the key molecular determinants responsible for channel activation. In addition, we explain the insensitivity of mouse TRPM4 to NC1 and pinpoint specific residues that define NC1 specificity for human TRPM4. Given the upregulation of TRPM4 in various human cancers, our mechanistic insights into NC1 activation and specificity provide a framework for the potential development of cancer therapeutics targeting TRPM4-mediated necrosis.

biophysics↗

bioRxiv2026

Disruption of the VEGFR3-HSPG2 induces lymphatic reflux dysfunction and sepsis

The lymphatic system plays a central role in fluid transport and immune regulation, yet its contribution to sepsis remains incompletely understood. Analysis of more than 500,000 individuals from the UK Biobank reveals that lymphatic system disorders and genetic variants in FLT4 (VEGFR3) are strongly associated with increased sepsis risk. Single-cell RNA sequencing further shows a marked reduction of VEGFR3^high lymphatic endothelial cells during sepsis. LEC-specific deletion of VEGFR3 impairs lymphatic reflux without disrupting vessel architecture, leading to barrier failure, systemic inflammation, bacterial dissemination, and sepsis. Mechanistically, VEGFR3 sustains lymphatic glycocalyx integrity by promoting SOX18-dependent HSPG2 transcription and heparan sulfate biosynthesis. Consistently, LEC-specific HSPG2 knockdown or pharmacological inhibition of SOX18 phenocopies VEGFR3 deficiency, whereas heparan sulfate supplementation alleviates sepsis-like pathology. Moreover, HSPG2 genetic variants are significantly associated with both lymphatic disorders and sepsis. Collectively, these findings identify lymphatic reflux dysfunction as a pathogenic determinant of sepsis and establish disruption of the VEGFR3-SOX18-HSPG2-heparan sulfate axis as an active driver of disease.

molecular biology↗

bioRxiv2026

Radiosynthesis and Evaluation of Novel Cholesterol 24-Hydroxylase Positron Emission Tomography Tracers

Cholesterol 24-hydroxylase (CH24H or CYP46A1) is a pivotal enzyme in brain cholesterol metabolism and has emerged as a therapeutic and imaging target in neurodegenerative disorders. Although [18F]Cholestify ([18F]CHL-2205) has shown promise as a positron emission tomography (PET) tracer for imaging of CYP46A1, the impact of cyclopropyl moiety conformation on binding and imaging performance remains unexplored. Here, we report the rational design and preliminary evaluation of novel CYP46A1 PET tracers, in which the left-side cyclopropyl group was modified into bridged, spirocyclic, and fused bicyclic architectures to probe steric and conformational effects. All compounds 9-11 exhibited high CYP46A1 affinity (IC50 = 0.19-0.28 nM). Radiosynthesis of [18F]9-11 was achieved via copper-mediated [18F]fluorination, providing practical non-decay-corrected radiochemical yields of 10-34% with excellent radiochemical purity (>98%). In vitro autoradiography in rat brain sections demonstrated specific and regionally selective binding, comparable to that observed for [18F]CHL-2205. These cyclopropyl-derived scaffolds establish a scaffold-driven strategy for PET tracer development, providing a robust framework for further structure-activity relationship studies and the rational optimization of CYP46A1 PET tracers.

pharmacology and toxicology↗

bioRxiv2026

Histology-Aware Graph for Modeling Intercellular Communication in Spatial Transcriptomics

Cell-cell communication (CCC) is essential to how life forms and functions. Recent tools achieve single-cell-resolved CCC inference utilizing spatial transcriptomics (ST). However, most ignore the modeling of tissue contexts surrounding cells, causing high false-positive/negative rates. Here, we propose HARMONIC, a CCC inference method integrating multimodal ST and hematoxylin and eosin (H&E)-stained images. HARMONIC causally modeling the transcriptomic-to-contextual relationships for CCC inference. The state-of-the-art performance was verified across ST platforms, species and healthy/diseased status, on both synthetic and biological samples. HARMONIC was applied in various real-world scenarios, especially on tissues with clear morphological boundaries, including cortical layers in mouse brain, medullary-cortex structures in mouse kidney, as well as tumor-stromal/immune interface. Significant refinement of false-positive/negative predictions was observed compared to ST-only CCC tools.

bioinformatics↗

bioRxiv2026

Critical role of cell competition in gliomagenesis

ABSTRACTMalignant glioma is incurable. Using a mouse genetic mosaic system to generate sporadic Trp53,Nf1-null OPCs, we previously identified oligodendrocyte precursor cell (OPC) as a cell-of-origin of glioma. Here, we report that pre-malignant Trp53,Nf1-null OPCs outcompete wildtype counterparts during their expansion. Blocking competition by mutating/strengthening wildtype OPCs impeded both pre-malignant progression and malignant expansion of glioma. "In-tissue" phosphoproteomic profiling revealed an enrichment of phosphopeptides related to RNA splicing and protein translation at the peak of cell competition, suggesting that competitiveness may stem from unique protein species. Among candidates was mTORC1, whose pharmacological inhibition or genetic disruption resulted in a loss of competitiveness in our mouse model. Finally, analysis of patient biopsies and interrogating the role of individual gliomagenic mutations in OPC competition supported its relevance in human gliomas. Together, these findings identified the driving role of competitive interactions among OPCs in gliomagenesis, and suggest unconventional therapeutic strategies to target this process.

cancer biology↗