Biology subjects

Teng, X.

Publications and source records attributed to Teng, X..

At least 19 recordsLinked to original sources

bioRxiv2026

Auditory tracking magnitude, temporal alignment, and anatomical distribution during wakefulness and propofol-based anesthesia in human sEEG

General anesthesia attenuates auditory responses, but response magnitude alone does not describe how residual activity aligns with sound over time or varies across the brain. We jointly characterized these aspects of auditory tracking using stereoelectroencephalography (sEEG) in 13 patients with drug-resistant epilepsy during wakefulness and clinically defined unresponsiveness under propofol-based anesthesia. The same rhythmic humming sequences were presented at approximately 1.61 Hz in both sessions. During anesthesia, stimulus-rate power showed widespread reductions and phase alignment with the stimulus rhythm was less consistent, although responses remained detectable at some recording channels. During wakefulness, response strength decreased with cortical surface distance from posteromedial Heschl's gyrus; this distance-response relationship was weaker during anesthesia. In a contrastive learning analysis (CEBRA), low-dimensional embeddings derived from anesthesia recordings yielded lower acoustic-envelope decoding accuracy on held-out data and lower consistency across model fits. Together, these findings characterize how attenuated auditory tracking is expressed jointly in response magnitude, temporal alignment, and anatomical distribution.

neuroscience↗

bioRxiv2026

Pervasive historical introgression across oak phylogeny shapes gene expression

Oaks were once described as the "worst-case scenario" for the biological species concept because of the presumed pervasive hybridization and introgression among species. However, we still lack a full picture of genome-wide introgression across the eight sections of the Quercus phylogeny. Furthermore, we still do not have a complete characterization of what is introgressed and how it functionally influences the recipient species. Firstly, we used 168 whole genomes from 67 Quercus species belonging to the eight sections of the Quercus phylogeny and a super pan-genome to generate a phylogeny and test for ILS and introgression. Introgression was widespread: ancient introgression occurred between ancestors of the eight sections and more recent introgression took place within sections. Secondly, using genome-wide transcriptome, methylome, and chromatin accessibility data from a subset of 19 species sampled from four sections we demonstrated that introgressed genes are more highly and uniformly expressed than non-introgressed ones. This difference in expression level between introgressed and non-introgressed genes mostly results from cis-regulation, and is most likely due to DNA methylation decay in promoter ACRs. In summary, introgression has been a major evolutionary force during the whole evolutionary history of Quercus and had a significant impact on fundamental processes such as gene regulation and expression.

evolutionary biology↗

bioRxiv2026

A Moonlighting Function of Kinetochore Complex Proteins in Golgi Assembly of Neural Stem Cells

Kinetochores play an essential role in mitosis, and human kinetochore variants are associated with microcephaly. However, their functions in quiescent/interphase cells are unknown. Here, we demonstrate that Drosophila kinetochore proteins promote the reactivation of quiescent NSCs and their regeneration upon injury by organizing Golgi-dependent acentrosomal microtubules. Drosophila kinetochore proteins localize to the Golgi vicinity in quiescent NSCs and are required for proper localization of Golgi proteins, including the Golgi-resident small GTPase Arf1 known to regulate quiescent NSC reactivation and regeneration. Moreover, Drosophila kinetochore proteins physically associate with Arf1 and function upstream of it during reactivation. Remarkably, human kinetochore protein SPC25 localizes to Golgi in interphase NSCs and HEK293T cells. Furthermore, human kinetochores have a conserved function in promoting Golgi organization and, in turn, microtubule dynamics, in interphase cells. Together, our findings reveal a conserved moonlighting role for kinetochores in Golgi assembly in quiescent Drosophila NSCs and human interphase cells.

neuroscience↗

bioRxiv2026

Single cell eQTL mapping reveals convergent glial-neuronal risk architecture in Parkinson's disease

Synucleinopathies affect [~]15 million people and are classically divided into neuronal (Parkinsons disease (PD), dementia with Lewy bodies) and glial (multiple system atrophy) disorders. Here we challenge this dichotomy. We functionally fine-map 90 PD GWAS signals across nine cell types in cortex and substantia nigra using disease-context, population-scale single-nucleus eQTL meta-analysis (N = 1,197), bulk brain eQTL analysis (N = 1,182), and Mendelian randomization. A stringent causal framework integrates single-nucleus allelic imbalance (snASE) with orthogonal validation. We identify 125 functional risk genes for 50 loci--nearly doubling supported genes--and assign genes and cell types to over half of GWAS signals. Unexpectedly, 51% of risk genes are regulated in glia, particularly oligodendrocytes and their precursors. Across cell types, risk converges on a shared glial-neuronal vesiculopathy network. These findings uncover a convergent glial-neuronal risk architecture and establish a single-cell atlas for context-aware gene discovery and precision therapeutics for PD.

genetics↗

bioRxiv2026

Immune reprogramming of 3D tumor models via optoporation-mediatedtargeted gene delivery to macrophages

The dynamics of the tumor microenvironment (TME) are a key determinant of cancer progression and therapeutic resistance through complex interactions between tumor, stromal and immune cell populations. Among these, tumor-associated macrophages (TAMs) play a central role in promoting tumor growth and immune suppression. However, the specific contributions of TAMs remain poorly understood due to the lack of tools enabling selective genetic manipulation in three-dimensional (3D) tumor models. Here, we present a gold nanoparticle-assisted optoporation approach that enables spatially selective plasmid-based gene delivery to TAMs within intact heterocellular 3D pancreatic ductal adenocarcinoma (PDAC) spheroids, thereby modulating the TME. In two-dimensional (2D) TAM cultures, conventional transfection of IRF5- and IKBKB-encoding plasmids validated their capacity to induce TAM repolarization, as evidenced by activation of interferon signaling. Extending this approach to 3D PDAC spheroids, nanoparticle-assisted optoporation achieved selective transfection of TAMs with IRF5- and IKBKB-encoding plasmids by transiently generating nanoscale membrane pores in illuminated cells. TAMs transfection elicited a robust interferon response, marked by transcriptional upregulation of IFNA, IFNB1, and CXCL10, and increased protein levels of IFNB1, IFNL1, and CXCL13, together with downregulation of pro-tumorigenic markers CEACAM5, IL19, and IL32. These coordinated changes indicate a shift towards an anti-tumorigenic TME. By enabling minimally invasive, TAM-specific gene delivery in complex multicellular 3D spheroids, this strategy allows precise modulation of the TME and opens new avenues for modeling its dynamics in cancer progression and therapeutic response.

bioengineering↗

bioRxiv2026

Unwinding of RNA G-quadruplexes induces mouse and human totipotency

Totipotent stem cells (TotiSCs) have significant application prospects in regenerative medicine and assisted reproductive technologies. The mRNAs of totipotency-related genes are rich in G-quadruplex (G4) structures, while the G4 density of pluripotency-related genes mRNAs is relatively low, suggesting a potential functional link between RNA G4s and the totipotent state. Nevertheless, how G4s are involved in the establishment or maintenance of mouse and human totipotency remains poorly understood. Here, we demonstrate that FC3, a small-molecule RNA G4 unwinder, enables efficient induction and maintenance of mouse and human TotiSCs (mG4TotiSCs and hG4TotiSCs). These FC3-induced TotiSCs closely recapitulate the molecular features of 2-cell-stage blastomeres via transcriptomic and epigenomic profiling. Functionally, both mG4TotiSCs and hG4TotiSCs exhibit totipotent capacity: they differentiate into embryonic and extraembryonic lineages in vitro and in chimeric embryos; moreover, they autonomously self-organize into blastocyst-like structures without exogenous signalling. Mechanistically, we identify that Gata2 mRNA, a G4-containing transcript, is essential for FC3-mediated reprogramming. Genetic disruption of Gata2 would abolish totipotency induction. Collectively, RNA G4 unwinding is a new regulatory axis governing totipotency acquisition and maintenance, providing insight into the functional interplay between nucleic acid secondary structures and cell fate plasticity.

cell biology↗

bioRxiv2026

Cryo-EM reveals the structural basis of subtype-specific, noncompetitive inhibition of the human P2X3 receptor

P2X receptors are ATP-gated cation channels, and the P2X3 subtype plays crucial roles in peripheral sensory neurons, including in chronic pain and chronic cough. Accordingly, P2X3 has attracted substantial interest as a therapeutic target. Gefapixant, a negative allosteric modulator (NAM) of P2X3, has been approved in some countries for the treatment of chronic cough; however, its limited selectivity for P2X3 homomers over P2X2/P2X3 heteromers is associated with taste disturbance as a prominent adverse effect. These limitations have motivated the development of next-generation NAMs with improved subtype selectivity, but their subtype-specific allosteric inhibition mechanisms are unclear. Here, we report the cryo-EM structure of the human P2X3 receptor in complex with ATP and the P2X3-selective next-generation NAM sivopixant, an investigational drug. Sivopixant binds to an allosteric site at the portal of the central pocket in the extracellular domain, and structure-based mutational analysis by electrophysiology identifies key residues required for sivopixant-dependent inhibition of human P2X3. Comparisons with P2X structures from other subtypes, together with gain-of-function mutants, define a structural basis for subtype-selective allosteric inhibition of the P2X3 receptor. Furthermore, structural comparisons with apo and ATP-bound open states of P2X3 receptors, together with molecular dynamics simulations, revealed that sivopixant expands the upper body domain to suppress the lower-body movements required for channel activation, thereby preventing channel opening even in the presence of ATP.

biophysics↗

bioRxiv2025

Automatic binding of basic sensory features requires consciousness

Conscious awareness requires establishing coherent percepts. Yet, whether consciousness is necessary for initiating the integration of basic sensory features remains unclear. Competing theories implicate distinct functional regimes of consciousness in the process of feature binding and creating conscious percepts. We used a novel multi-feature oddball paradigm with intracranial stereo-electroencephalography (sEEG) recordings in awake and anesthetized states to investigate the functional boundary of consciousness. In the awake state, the auditory attributes of loudness and tone, as well as the binding of the two features, were automatically encoded without attention to the stimuli in a functionally localized sensory cortical network. In the anesthetized state, the cortical registration of single attributes was preserved, whereas the binding was abolished. Moreover, anesthesia mostly influenced later cortical processes after stimuli offset. These results reveal the borderline of exertion of consciousness between the encoding and manipulation of basic sensory features in local cortical circuits - the functional boundary of consciousness constrains the feedforward binding and recurrent process directly at local rather than global level computations.

neuroscience↗

bioRxiv2025

Mid-Infrared Photothermal Imaging of Fatty Acid Desaturation Reaction in Cancer Cells

Direct visualization of metabolic conversions within living systems is essential for understanding metabolic activities yet challenging due to the absence of reaction-specific reporters and the limited sensitivity of current imaging modalities. Herein, we report an approach to monitor fatty acids (FAs) desaturation, primarily catalyzed by stearoyl-CoA desaturase, in cancer cells using deuterium (D)-labeled palmitic acid (PA-d31) as the reaction-specific reporter and mid-infrared photothermal (MIP) microscopy as the bond-selective imaging modality. The desaturation of PA-d31 produced a peak at 2246 cm-1 in the cell-silent region, corresponding to the stretching vibration of unsaturated C-D bonds (D-C=C-D) in unsaturated fatty acids. Penalized least squares fitting was employed to remove water background for enhancing the visibility of this peak. Our study revealed heterogeneous spatial distributions of both saturated FAs and their desaturated metabolites within lipid droplet pools in cancer cells. Furthermore, we observed an increase in fatty acid unsaturation level in OVCAR5 cells under cisplatin-induced stress. By directly visualizing fatty acid desaturation, this study offers new insights into fatty acid metabolism and opens avenues for evaluating new therapeutic strategies targeting fatty acid metabolism.

biochemistry↗

bioRxiv2025

Eye blinks synchronize with musical beats during music listening

Auditory-motor synchronization, the alignment of body movements with rhythmic patterns in music, is a universal human behavior, yet its full scope remains incompletely understood. Through four experiments with 123 young non-musicians, integrating eye-tracking, neurophysiological recordings, white matter structural imaging, and behavioral analysis, we reveal a previously unrecognized form of synchronization: spontaneous eye blinks synchronize with musical beats. Blinks robustly synchronized with beats across a range of tempi and independently of melodic cues. EEG recordings revealed a dynamic correspondence between blink timing and neural beat tracking. Individual differences in blink synchronization were linked to white matter microstructure variation in the left arcuate fasciculus, a key sensorimotor pathway. Additionally, the strength of blink synchronization reflected the modulation of dynamic auditory attention. These findings establish blink synchronization as a novel behavioral paradigm, expanding the auditory-motor synchronization repertoire and highlighting the intricate interplay between music rhythms and oculomotor activity. This discovery underscores a cross-modal active sensing mechanism, offering new insights into embodied music perception, rhythm processing, and their potential clinical applications.

neuroscience↗

bioRxiv2024

ARHGAP12 suppresses F-actin assembly to control epithelial tight junction mechanics and paracellular leak pathway permeability

Tight junctions (TJ) separate body compartments and control the paracellular transport of ions, solutes, and macromolecules across epithelial barriers. There is evidence that claudin-based ion transport (the pore pathway) and the paracellular transport of macromolecules (the leak pathway) are independently regulated processes. However, how leak pathway permeability is controlled is not well understood. Here we have identified the Cdc42/Rac GTPase activating protein ARHGAP12 as a novel and specific regulator of the leak pathway. ARHGAP12 is recruited to TJ via an interaction between its SH3 domain and the TJ protein ZO-2. Using a combination of biochemical and biophysical approaches, in vitro actin polymerisation assays, and permeability assays in MDCK-II cells, we show that ARHGAP12 suppresses N-WASP-mediated F-actin assembly at TJ to dampen junctional tension. This promotes paracellular leak pathway permeability without affecting ion flux. Mechanistically, we demonstrate that the ARHGAP12 tandem WW domain interacts directly and in a multivalent manner with an array of PPxR motifs in the proline-rich domain of N-WASP. This interaction is sufficient to suppress SH3 domain-mediated N-WASP oligomerisation and Arp2/3-driven F-actin assembly in vitro. Collectively our data demonstrate a critical role for ARHGAP12 in suppressing junctional F-actin assembly and tension to promote the flux of small macromolecules across the TJ.

cell biology↗

bioRxiv2024

Therapeutic Peptide SS-31 Modulates Membrane Binding and Aggregation of Alpha-Synuclein and Restores Impaired Mitochondrial Function

Membrane binding and aggregation properties of -synuclein are closely associated with Parkinsons disease and a class of related syndromes named as synucleinopathy. This study explored the potential of SS-31 (Elamipretide), a therapeutic tetrapeptide with alternating cationic and aromatic residues and known properties of mitochondrial inner membrane binding and oxidative stress reduction, in modulating -synuclein interaction with the lipid membranes and mitigating impairment of mitochondrial function induced by -synuclein oligomers. It was demonstrated by both fluorescence correlation spectroscopy and fluorescence anisotropy that SS-31 displaces both wild-type and N-terminus acetylated -synuclein from negatively charged small unilamellar vesicles in a dose-dependent manner. Thioflavin-T assay and transmission electron microscopy (TEM) showed that SS-31 inhibits membrane-induced -synuclein aggregation and alters the morphology of -synuclein fibrils. Moreover, Seahorse Mito Stress Test indicated that SS-31 restores impaired mitochondrial function in -synuclein oligomer-treated neuroblastoma cells. Finally, confocal imaging revealed that SS-31 hinders cellular uptake of -synuclein oligomers, possibly by modifying cell membrane electrostatics. These findings underscore the multifaceted protective role of SS-31 against mitochondrial dysfunction caused by -synuclein aggregation. Consequently, SS-31 emerges as a promising therapeutic candidate to attenuate neurodegeneration pertinent to -synuclein misfolding and aggregation. There is a good potential for further refinement of such peptide against many diseases linked to mitochondrial dysfunction and oxidative stress.

biochemistry↗

bioRxiv2024

Eyes robustly blink to musical beats like tapping

Auditory-motor synchronization with musical rhythm may extend beyond overt body movements like fingers or feet. Through four experiments combining eye-tracking, neurophysiological and structural imaging approaches with 123 young non-musicians, we demonstrated robust synchronization of spontaneous eye blinks with musical beats. The blinking rate consistently aligned with the beat rate across various tempi and independent of melodic cues. Blinking exhibited beat phase-specific tuning, with inhibition immediately before beats and increased frequency afterward. Variations in blink-beat synchronization corresponded to the difference in microstructural lateralization of auditory-parietal connectivity. EEG recordings revealed a dynamic correspondence between blink and neural beat tracking. Mechanistically, this synchronization reflects dynamic auditory attention and temporal modulation of visual sampling. Our findings establish eye tapping as a novel behavioral paradigm, expanding the behavioral repertoire of auditory-motor synchronization. It underscores the intricate relationship between music rhythms and peripheral oculomotor system, proposing a cross-modal active sensing and embodied experience in music perception.

neuroscience↗

bioRxiv2024

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling

The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasis. Defects in NSC reactivation are associated with neurodevelopmental disorders. Drosophila quiescent NSCs extend an actin-rich primary protrusion toward the neuropil. However, the function of the actin cytoskeleton during NSC reactivation is unknown. Here, we reveal the fine F-actin structures in the protrusions of quiescent NSCs by expansion and super-resolution microscopy. We show that F-actin polymerization promotes the nuclear translocation of Mrtf, a microcephaly-associated transcription factor, for NSC reactivation and brain development. F-actin polymerization is regulated by a signaling cascade composed of G-protein-coupled receptor (GPCR) Smog, G-protein q subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.

developmental biology↗

bioRxiv2023

Molecular mechanism of α-synuclein aggregation on lipid membranes revealed.

The central hallmark of Parkinsons disease pathology is the aggregation of the -synuclein protein, which, in its healthy form, is associated with lipid membranes. Purified monomeric -synuclein is relatively stable in vitro, but its aggregation can be triggered by the presence of lipid vesicles. Despite this central importance of lipids in the context of -synuclein aggregation, their mechanistic role in this process has not been established to date. Here, we use chemical kinetics to develop a detailed mechanistic model that is able to globally describe the aggregation behaviour of -synuclein in the presence of DMPS lipid vesicles, across a range of lipid and protein concentrations. Through the application of our kinetic model to experimental data, we find that the reaction is a co-aggregation process involving both protein and lipids and that lipids promote aggregation predominantly by enabling the elongation process. Moreover, we find that the initial formation of aggregates, via primary nucleation, takes place not on the surface of lipid vesicles but at the interfaces present in vitro. Our model will enable mechanistic insights, also in other lipid-protein co-aggregation systems, which will be crucial in the rational design of drugs that inhibit aggregate formation and act at the key points in the -synuclein aggregation cascade.

biophysics↗

bioRxiv2023

Structural insights into the allosteric inhibition of P2X4 receptors

P2X receptors are ATP-activated cation channels involved in a variety of physiological functions. Among the seven subtypes of P2X receptors, the P2X4 subtype plays important roles in both the immune system and the central nervous system, particularly in neuropathic pain. Therefore, P2X4 receptors are of increasing interest as potential drug targets, and several P2X4 subtype-specific inhibitors have been developed. However, the mechanism of allosteric inhibition of P2X4 receptors remains largely unclear due to the lack of structural information. Here, we report the cryo-EM structures of the zebrafish P2X4 receptor in complex with two P2X4 subtype-specific antagonists, BX430 and BAY-1797. Both antagonists bind to the same allosteric site located at the subunit interface at the top of the extracellular domain. Structure-based mutational analysis by electrophysiology identified the important residues for the allosteric inhibition of both zebrafish and human P2X4 receptors. Interestingly, in the previously reported apo structure, the binding pocket is closed and too narrow to accommodate allosteric modulators. Structural comparison revealed the ligand-dependent structural rearrangement of the binding pocket to stabilize the binding of allosteric modulators, which in turn would prevent the structural changes of the extracellular domain associated with channel activation. Furthermore, comparison with the previously reported P2X structures of other subtypes provided mechanistic insights into subtype-specific allosteric inhibition. Overall, the present work provides structural insights into the allosteric inhibition mechanism of P2X4 receptors, facilitating the design and optimization of specific modulators for P2X4 receptors.

biophysics↗

bioRxiv2023

Collagen co-localised with macrovesicular steatosis for fibrosis progression in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a commonly occurring liver disease; however, its exact pathogenesis is not fully understood. The purpose of this study was to quantitatively evaluate the progression of steatosis and fibrosis by examining their distribution, morphology, and co-localisation in NAFLD animal models. qSteatosis showed a good correlation with steatosis grade (R: 0.823-0.953, P<0.05) and demonstrated high performance (area under the curve [AUC]: 0.617-1) in all six mouse models. Based on their high correlation with histological scoring, qFibrosis containing four shared parameters were selected to create a linear model that could accurately identify differences among fibrosis stages (AUC: 0.725-1). qFibrosis co-localised with macrosteatosis generally correlated better with histological scoring and had a higher AUC in all six animal models (AUC: 0.846-1). Quantitative assessment using second-harmonic generation/two-photon excitation fluorescence imaging technology can be used to monitor different types of steatoses and fibrosis progression in NAFLD models. The collagen co-localised with macrosteatosis could better differentiate fibrosis progression and might aid in developing a more reliable and translatable fibrosis evaluation tool for animal models of NAFLD.

pathology↗

bioRxiv2022

Golgi-dependent Reactivation and Regeneration of Quiescent Neural Stem Cells

The ability of stem cells to switch between quiescent and proliferative states is crucial for maintaining tissue homeostasis and regeneration. In Drosophila, quiescent neural stem cells (qNSCs) extend a primary protrusion, which is removed prior to NSC reactivation. Here, we have unravelled that qNSC protrusions can be regenerated upon injury. This regeneration process relies on the Golgi apparatus which acts as the major acentrosomal microtubule-organizing centre in qNSCs. A Golgi-resident GTPase Arf1 and its guanine-nucleotide exchange factor Sec71 promote NSC reactivation and regeneration via the regulation of microtubule growth. Arf1 physically associates with its new effector Mini Spindles (Msps)/XMAP215, a microtubule polymerase. Finally, Arf1 functions upstream of Msps to target the cell-adhesion molecule E-cadherin to NSC-neuropil contact sites during NSC reactivation. Our findings have established Drosophila qNSCs as a new regeneration model and identified a novel Arf1/Sec71-Msps pathway in the regulation of microtubule growth and NSC reactivation.

cell biology↗