Biology subjects

Chang, L.

Publications and source records attributed to Chang, L..

At least 19 recordsLinked to original sources

bioRxiv2026

MR-Guided Focused Ultrasound Neuromodulation of Nucleus Accumbens to Attenuate Oral Fentanyl Motivation in A Self-Administration Rat Model

Introduction: Transcranial low-intensity focused ultrasound (LIFU) is being explored as a non-invasive approach for neuromodulation to treat opioid use disorder (OUD). Methods: We evaluated MR-guided focused ultrasound, with LIFU, targeting nucleus accumbens (MRgLIFU-NAc) bilaterally, using MR-acoustic radiation force-imaging (MR-ARFI) to ensure accurate targeting and adjust for FUS intensity delivered at the target. Male and female rats were trained to self-administer fentanyl/sucrose (70ug/ml fentanyl citrate in 5% sucrose) or 5% sucrose alone. Three cohorts of rats (total n=76) were evaluated on progressive ratio (PR) responding for oral fentanyl/sucrose at either 4 or 24 hours post-MRgLIFU-NAc. Animals in the first two cohorts received repeated rounds of LIFU or sham (anesthesia-duration matched). In cohort 3, we used a counterbalanced within-subjects design in which rats received both LIFU and sham one week apart. Results: Reducing sucrose concentrations decreased responding for sucrose alone more than for fentanyl/sucrose, demonstrating a role for fentanyl in the reinforcing properties of fentanyl/sucrose. Across three sonication schemes, MRgLIFU-NAc did not attenuate PR performance for oral fentanyl/sucrose at 4 or 24-hours post-LIFU relative to controls. Adjusting LIFU intensity with MR-ARFI did not correlate with changes in PR from baseline. We confirmed that NAc is the correct target by bilateral inactivation of NAc with muscimol/baclofen mixture (50 + 50 ng/side), which reduced PR responding for fentanyl/sucrose. Conclusion: The three sets of LIFU parameters, with repeated MRgLIFU-NAc sessions, did not produce detectable changes in oral fentanyl/sucrose motivation. Further studies are required to determine effective LIFU parameters needed to reduce NAc-dependent fentanyl motivation.

neuroscience↗

bioRxiv2026

Design of readers for pathological PTM proteoforms in Alzheimer's disease

Alzheimer's disease (AD) is characterized by heterogeneous Tau phosphorylation and aberrant amyloid-beta (Abeta) processing, yet molecular tools that distinguish closely related molecular states of tau and Abeta with predefined specificity remain difficult to develop. Here, we designed de novo protein readers targeting three disease-associated phospho-Tau regions and N-terminal pyroglutamate-modified Abeta (N3pG-Abeta). Screening 192 designs per target identified 51 modification-selective hits among 768 candidates (6.6%). Representative readers exhibited nanomolar to subnanomolar affinities for modified peptides, discriminated authentic modifications from unmodified or substitution-based controls, and preferentially recognized modified full-length targets. We further programmed local modification specificity by interface redesign, generating pT231 readers conditional on the phosphorylation state of neighboring S235 and S237. A 2.0-angstrom crystal structure of an N3pG-Abeta reader closely matched the computational design model (interface C-alpha RMSD = 0.52 angstrom), and redesign of pT231 readers tuned apparent binding affinities from greater than 1 uM to below 1 nM. In a human 3D neuronal culture with both pathological Abeta and tau, selective readers targeting N3pG-Abeta, Tau pT231, and Tau pT217 recognized disease-associated signals, exhibiting colocalization with related antibodies and much higher signal in the AD line than the control. Tau pT231 readers further quantitatively distinguish AD patients and control human brain lysates in dot-blot assays. Together, these results establish genetically encoded readers with programmable specificity for defined Tau and Abeta modification states, enabling molecular-state-resolved detection in human disease models and biological samples, and lay a foundation for controlled pathological molecular perturbation.

bioengineering↗

bioRxiv2026

Structural and genetic dissection of RNA-guided gene repression by TnpB-derived transcription factors

TnpB nucleases, the evolutionary progenitors of CRISPR-associated Cas12 enzymes, are transposon-encoded, RNA-guided endonucleases found throughout bacteria. Independent of the trajectory towards adaptive immunity, TnpB nucleases have also recurrently given rise to TnpB-like nuclease-dead repressors (TldRs), a family of programmable RNA-guided transcription factors, though the physiological roles of most TldR clades remain unclear. Recently, we identified a TldR clade associated with bacterial ABC transporter operons, but this clade has not been characterized in any native host, leaving the biological significance of its predicted regulatory function unknown. Here, we demonstrate direct in vivo repression of the oligopeptide permease (opp) binding protein OppA in Enterococcus faecalis, implicating TldR in shaping the substrate repertoire of bacterial peptide import machinery. Phylogenetic and comparative genomic analyses reveal that bacterial genomes typically encode multiple, structurally conserved but functionally diversified OppA paralogs, suggesting that TldR-mediated repression could enable selective tuning of transporter composition. To define the structural basis of this regulatory specificity, we used cryo-electron microscopy to capture an oppF-associated TldR in multiple functional states, revealing a conserved bilobed architecture and a TAM recognition mechanism inherited from TnpB ancestors. Together, these findings define the structural, genetic, and evolutionary basis of a widespread RNA-guided regulatory system domesticated from mobile genetic elements to tune peptide transport in bacteria.

microbiology↗

bioRxiv2026

An Artificial Intelligence Model for Longitudinal Assessment of TCR Repertoires in SARS-CoV-2 Vaccine Recipients

T cells play a crucial role in reducing disease severity during SARS-CoV-2 infection and in shaping long-term immune memory. However, the precise molecular immune responses, particularly involving T-cell receptor (TCR) repertoire changes after full vaccination, and the use of TCR analysis to evaluate vaccine efficacy, remain incompletely understood. In this study, we developed the DeepAir-Cov19 model (AUC=0.94), a large language model tailored to identify SARS-CoV-2-specific TCRs, and observed significant differences in the TCR profiles between antibody-negative and antibody-positive populations before and after vaccination, indicating that the immune status of pre-vaccine recipients can directly assess the efficacy of vaccination. Notably, SARS-CoV-2-specific TCRs expanded to peak levels after the second dose and remained detectable in most subjects up to 10 months post-vaccination. Meanwhile, we also identified three specific V genes, 20 V-J combinations, and 3 epitopes associated with these responses. Finally, by leveraging vaccine-specific TCRs as novel biomarkers, we developed a vaccine efficacy model that predicts antibody levels with a mean AUC of 0.96. These findings underscore the accuracy of the large model in predicting SARS-CoV-2-specific TCRs and reveal a strong correlation between SARS-CoV-2-specific TCR responses and antibody levels. This highlights the complementary and synergistic roles of T cells and antibodies in providing vaccine-mediated protection. Our results offer valuable insights into the longitudinal dynamics of SARS-CoV-2-specific TCRs and illustrate the potential for developing potency evaluation models based on these TCR insights.

bioinformatics↗

bioRxiv2026

Ex vivo glioblastoma migration phenotypes define clinical recurrence and tumor heterogeneity

Glioblastoma's pronounced migratory capacity underlies its diffuse invasion, presenting a formidable barrier to successful treatment. Ex vivo characterization of glioblastoma cells isolated from freshly resected clinical samples under physiologically relevant conditions revealed two distinct migratory phenotypes, Fast Migrating (FM) and Slow Migrating (SM). These phenotypes reflect distinct mechanosensitivity profiles and are associated with pharmacological responses that support the motor clutch model of cell migration. Analysis of genes associated with these phenotypes revealed a transcriptomic signature that closely associated with in vitro cell migration, histological invasion in patient specimens, and clinical survival. Single-nucleus RNA sequencing revealed that FM and SM cells coexist within a single glioblastoma, with FM cells enriched at the periphery and SM cells localized to the tumor core. Collectively, our study demonstrates the utility of ex vivo glioblastoma characterization, allowing decoding of tumor heterogeneity and clinical prognostication as well as providing a framework for deconvoluting the complex cancer phenotype.

cancer biology↗

bioRxiv2026

A vascular chip for disease-relevant flow shear stress topology

Vascular chips have advanced endothelial mechanobiology by enabling controlled responses to hemodynamic cues, yet disease-relevant wall shear stress (WSS) modeling remains limited. Simplified one-dimensional flow shear systems, designed mainly for physiological mechanobiology, miss the topological organization of pathological flow, whereas patient-specific vascular models capture complex hemodynamics but sacrifice generality and imaging compatibility. Here we develop a programmable vascular chip that converts disease-associated WSS topology into a physiologically parameterized experimental input. The device reconstructs a representative pathological shear-topology field on endothelial layer, supports stationary and physiologically paced oscillatory flow modes, and integrates matched unidirectional-shear references within the same chip. Using this system, we show that oscillatory WSS topology destabilizes endothelial monolayers, drives asymmetric collective emergent behaviors, impairs actin-nuclear mechanotransduction, accompanied by nuclear softening and enhanced perinuclear nanoparticle uptake. Integrated live-cell imaging, fluorescence analysis, Brillouin microscopy, and transport assays enable multimodal phenotyping across collective, subcellular mechanical and functional scales. By making disease-relevant WSS topology experimentally controllable, this vascular-chip framework bridges computational hemodynamics and experimental mechanomedicine, supporting standardized vascular disease modeling and functional screening.

bioengineering↗

bioRxiv2026

Dynamic resource allocation orchestrates physical simulation in the human brain

Humans can flexibly predict physical events by internally simulating object dynamics in the brain--a capacity lacking in current AI systems. Using a ball collision paradigm with visual occlusion combined with multimodal neuroimaging (fMRI/MEG), we uncover a spatiotemporally organized neural architecture for physical simulation. fMRI reveals hierarchical spatial segregation: higher-order cortical regions encode relational physical variables, distinct from object-specific features encoded in the lower-order sensorimotor regions. MEG uncovers two temporally distinct neural processes: a real-time simulation tracking the evolving state of the object, in alignment with collision dynamics, and an early predictive signal anticipating collision occurrence ([~]700 ms before contact). We propose that this early predictive control mechanism dynamically allocates cognitive resources during simulation. This is formalized by a Dynamic Resource Intuitive Physics Engine (IPE) model, which captures both behavioral data and the dual neural timescales by optimizing accuracy-cost tradeoffs. Crucially, this framework predicts early encoding of another adaptive control variable separate from collision occurrence, as evidenced by both MEG and pupillary responses. These findings reveal how the brain achieves efficient physical inference through hierarchically organized predictive control that dynamically allocates cognitive resources.

neuroscience↗

bioRxiv2026

DNA remodeling couples target recognition to directional transposition in a Tn7-like CAST

CRISPR-associated transposons (CASTs) couple target recognition to the insertion of large DNA cargoes, but how distinct targeting pathways are converted into productive and directional integration remains poorly understood1. Here we define the assembly pathway of a type I-B1 CAST from Anabaena variabilis, a system closely related to prototypical Tn7 that retains TnsD-mediated glmS recognition while incorporating CRISPR-based RNA-guided targeting2. Cryo-electron microscopy structures across multiple intermediates define a structural trajectory from two-step TnsD-mediated target recognition and stepwise assembly of the AAA+ ATPase TnsC to recruitment and activation of the split TnsA/TnsB transposase module. This trajectory culminates in an asymmetric strand-transfer complex that provides a structural basis for insertion orientation and supports a role for ATP hydrolysis in productive transpososome assembly. In parallel, RNA-guided targeting structures refine the functional PAM to ATG, define TniQ recruitment by Cascade, and show how CRISPR-based recognition converges on the shared TnsABC machinery. Together, these findings establish DNA remodeling and minor-groove positioning of TnsC as a common structural signal that converts protein- and RNA-guided target recognition into directional DNA insertion.

biochemistry↗

bioRxiv2026

Sex-Dependent Effects of Glutamatergic Disruption on Dopaminergic Neuron Subtype Vulnerable in Parkinson's Disease

Aldehyde dehydrogenase 1A1-positive (ALDH1A1+) dopaminergic neurons (DANs) are preferentially vulnerable in Parkinsons disease (PD), yet how their activity is modulated by presynaptic inputs remains poorly defined. Here we investigated the role of glutamatergic input by conditionally deleting Grin1, which encodes a critical NMDA receptor (NMDAR) subunit, in ALDH1A1+ DANs. Grin1 conditional knockout (cKO) mice displayed normal locomotion and motor learning; however, females exhibited enhanced operant reward acquisition and excessive feeding with transient weight gain following food restriction. To determine regional contributions, Grin1 was selectively knocked down in ALDH1A1+ DANs of either the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc). VTA-specific knockdown in females was sufficient to reproduce the post-restriction feeding and weight gain phenotype. Bulk whole-brain mRNA sequencing revealed pronounced sex-dependent transcriptional changes, primarily in female Grin1 cKO mice after food restriction. Many differentially expressed genes were associated with mitochondrial function, energy metabolism, and synaptic signaling. Together, these findings reveal a sex-specific role for NMDAR-mediated glutamatergic input to ALDH1A1+ VTA DANs in regulating feeding behavior, providing mechanistic insight into how dysfunction of this vulnerable subpopulation may contribute to PD-associated compulsive eating disorders. Key FindingDisrupted NMDA receptor-mediated glutamatergic input to ALDH1A1+ DANs drives sex-specific feeding abnormalities relevant to PD-associated compulsive eating disorders.

neuroscience↗

bioRxiv2026

Striatal FOXP2 is essential for stable vocal production in non-human primates

The transcription factor FOXP2 is the most well-known language-related gene in humans, yet its role in primate vocalization remains poorly understood. Here we report that knockdown of FOXP2 in the striatum markedly disrupts vocalization stability in the marmoset monkey, a valuable non-human primate model for studying vocal behavior. FOXP2 exhibited high expression in the marmoset striatum, especially during early development. Using the CRISPR-Cas12 system, we achieved specific in vivo editing of the FOXP2 gene and effective knockdown of FOXP2 protein expression in the marmoset striatum. Two neonatal marmosets received bilateral striatal injections of the gene-editing and control virus, respectively, and were raised together in the same family. In three such marmoset pairs, analysis of vocalizations recorded during 6-15 weeks post-injection revealed that striatal FOXP2 knockdown significantly altered vocal features and increased intra-individual variability in phee syllables--the most common marmoset vocalization, often produced repetitively as multi-syllable phee calls. Notably, in FOXP2-edited marmosets, acoustic alterations were minimal in the first syllable of phee calls but became progressively more pronounced in subsequent syllables, which exhibited a marked upward shift in the frequency spectrum over time with progressively steeper slopes. These temporal dynamics in vocal features reflect a reduction in the stability of continuous vocal production. In line with the known striatal functions in motor control, our findings provide the first evidence of FOXP2 in controlling vocalization in non-human primates, thereby opening new avenues for investigating the neural mechanisms underlying FOXP2 function.

neuroscience↗

bioRxiv2026

Coronavirus envelope protein drives iron sensing disorder by hijacking the TAp73-FDXR axis

Iron overload is increasingly recognized as a critical contributor to coronavirus pathogenesis1, yet the underlying induction mechanisms remain unclear. Here, we uncover a fundamental pathway by which coronavirus drives IRP1 RNA-binding activity to induce iron accumulation2 via targeting the TAp73-FDXR axis. Specifically, coronavirus infection represses transcription of FDXR (encoding the key rate-limiting enzyme in host iron-sulfur cluster synthesis3), thereby impairing host iron-sulfur cluster generation to trigger the functional conversion of the cytosolic aconitase 1 (ACO1) into iron-regulatory protein 1 (IRP1)4, ultimately leading to the hosts persistently false perception of iron deficiency. We identify TAp73 as the primary transcription factor governing FDXR expression, and demonstrate that the coronavirus envelope protein (CoV-E) orchestrates TAp73 nuclear export. Subsequently, CoV-E binds TAp73 through a critical valine residue within its C-terminal PBM domain, inducing the K48-linked ubiquitination and proteasomal degradation of TAp73. Furthermore, we developed a CoV-E-targeting molecule, DPTP-FC, which blocks CoV-E-TAp73 interaction via forming steric hindrance and effectively alleviates iron accumulation and tissue damage caused by PEDV, PDCoV, and SARS-CoV-2 infection. Our study reveals the central role of the TAp73-FDXR axis in CoV-induced iron accumulation, highlighting CoV-E as an attractive antiviral target and DPTP-FC as a promising therapeutic candidate.

microbiology↗

bioRxiv2026

Single-molecule spatial genomics reveals the multi-scale organization and plasticity of extrachromosomal DNA in glioblastoma

Extrachromosomal DNA (ecDNA) is a major driver of intratumoral heterogeneity and is associated with poor clinical outcomes across cancers, yet how individual ecDNA molecules are organized and regulated within intact tumors remains unknown. Here, we leveraged single-molecule, multi-modal spatial genomics to resolve the three-dimensional chromatin organization and transcriptional activity of individual EGFR-containing ecDNA molecules in glioblastoma (GBM) cells in vitro, in orthotopic xenografts, and in patient-derived GBM tissue. At the larger scale, we find that distinct GBM molecular and functional states emerge depending on the local cellular environment. EGFR expression was markedly different between GBM subpopulations, and perturbations of EGFR dosage shifted GBM cellular states. ecDNA expression was modulated by multiple mechanisms, including variation in copy number, chromatin organization, DNA sequence, and chromosomal reintegration, which were simultaneously measured within the same cells. At the single-molecule scale, ecDNA adopts a physically expanded chromatin configuration with larger ecDNA molecules having higher transcriptional activity and interaction with active transcriptional machinery. ecDNA regulation was coordinated within cells and across GBM states, and ecDNA copy number, structure, and transcription were spatially organized across the tumor architecture. Co-culturing GBM cells with neurons recapitulated key features of infiltrative regions, including lower EGFR expression, reduced ecDNA copy number, and increased chromosomal reintegration, suggesting a causal role for the microenvironment in shaping ecDNA regulation. Collectively, these findings support a model in which GBM states and ecDNA are linked, plastic, and influenced by microenvironmental contexts, revealing a previously inaccessible layer of genome organization underlying tumor heterogeneity and malignant cell behavior.

genomics↗

bioRxiv2026

Structural basis of caveolin-driven membrane bending

Caveolins are monotopic membrane proteins essential for caveolae formation and have key roles in signaling and lipid regulation. Caveolins assemble into amphipathic discs with a central {beta}-barrel, an architecture distinct from other membrane-remodeling proteins. These discs embed in the membrane inducing membrane curvature. However, the mechanism of disc-driven bending remains unresolved. Using cryo-electron tomography, structure-guided mutagenesis, and mammalian cell studies, we show that evolutionarily distinct caveolins differ dramatically in their ability to curve membranes despite their conserved architecture. Through computational and theoretical analyses, we demonstrate that patterning of hydrophobic residues along the rim of the disc of human Caveolin-1 induces the deformation of the surrounding leaflet, dictating membrane bending. Finally, we determine a 4.1[A] resolution structure of Caveolin-1 within heterologous caveolae in situ, showing the disc adopts a funnel-like conformation, further shaping membrane architecture. Together, these findings reveal fundamental structural principles that empower caveolins to sculpt and remodel cellular membranes.

cell biology↗

bioRxiv2026

Integrative Single-Cell Epigenomic Atlas Annotates the Regulatory Genome of the Adult Mouse Brain

Histone modifications underpin the cell-type-specific gene regulatory programs that drive the remarkable cellular diversity of the mammalian brain. Here, we jointly profiled four histone modifications and the transcriptome in 2.5 million nuclei from the adult mouse brain. By integrating these data with chromatin accessibility, DNA methylation, and three-dimensional genome organization, we constructed a unified epigenomic atlas spanning over 100 brain cell subclasses, and assigned active, primed, and repressive chromatin states across 81% of the genome. Active chromatin states marked by combinatorial histone modifications better nominate candidate enhancers with functional support than chromatin accessibility alone, while H3K27me3- and H3K9me3-marked chromatin states delineate distinct modes of cell-type-specific gene repression. Finally, this multimodal resource enables deep learning models that predict cell-type-specific epigenomic features and gene expression from DNA sequence, providing a comprehensive framework for annotating the brain regulatory genome and interpreting non-coding disease risk variants. HIGHLIGHTS- A single-cell epigenome atlas of transcription and four histone modifications across 2.5M mouse brain cells - Multimodal integration maps chromatin states across [~]81% of the adult mouse brain genome - Cell-type-resolved chromatin landscapes reveal regulatory programs mediated by enhancers, Polycomb and H3K9me3 - Deep learning models predict cell-type-specific epigenomic features and gene expression from DNA sequence

genomics↗

bioRxiv2026

Single-cell Multiome Analysis of Chromatin State and Transcriptome in the Human Basal Ganglia

The basal ganglia play essential roles in motor control, emotion, learning and reward processing. Their dysfunction contributes to many neurological and psychiatric disorders. However, the gene regulatory programs defining basal ganglia cell-type identity and function remain poorly understood, limiting interpretation of disease-associated non-coding variants. Here, we present the first single-cell multiome atlas of histone modifications and transcriptomes across eight basal ganglia regions from neurotypical adult human donors. Joint profiling reveals cell-type-specific deployment of active and repressive cis-regulatory elements and gene regulatory networks, and suggests a combinatorial homeobox transcription factor code underlying cell identity. Integration with matched spatial transcriptomic MERFISH data uncovers regional heterogeneity of epigenomic landscapes. Comparative analysis between human and mouse medium spiny neurons uncovers conservation of core gene regulatory features. This atlas interprets non-coding risk variants of neuropsychiatric disorders and supports the development of a deep learning model to predict gene regulation and functional effects of disease-associated variants. HIGHLIGHTSO_LIJoint single-cell profiling of transcriptomes and three histone modifications across eight human basal ganglia regions characterizes active and repressive chromatin states at cell-type resolution. C_LIO_LICell-type-specific gene regulatory programs decode combinatorial homeobox TF grammar governing the identity and diversification of basal ganglia neurons. C_LIO_LIIntergrative analyses link noncoding neuropsychiatric risk variants to specific cell types, regulatory elements, and candidate target genes. C_LIO_LIA sequence-to-function deep-learning model predicts gene regulation from DNA sequence and prioritizes functional disease-associated variants. C_LI

genomics↗

bioRxiv2026

Single-Cell Atlas of Transcription and Chromatin States Reveals Regulatory Programs in the Human Brain

Directly measuring chromatin states alongside transcription is essential for understanding how cell-type-specific regulatory programs are established and maintained in the adult human brain. We present a large-scale single-cell multimodal atlas generated by jointly profiling transcriptome with active (H3K27ac) and repressive (H3K27me3) histone modifications across 18 brain regions. We profile >750,000 nuclei spanning 160 cell types and integrate these data with chromatin accessibility, DNA methylation, 3D genome architecture, and spatial transcriptome. This framework annotates >500,000 regulatory elements and resolves cell-type-specific chromatin states. We link enhancers to target genes, infer gene regulatory networks, and classify chromatin interactions, revealing neuron-enriched long-range Polycomb repression of developmental genes. Integrating these maps with GWAS data and sequence-based model prioritizes noncoding variants, effector genes, and vulnerable cell types for neuropsychiatric disorders. Finally, cross-species comparisons show conserved activation but more divergent repression. Together, this study provides a functional reference for interpreting noncoding variants, epigenetic memory, and brain organization. HIGHLIGHTSO_LIJoint single-cell profiling of transcriptomes with active or repressive histone modification in >750,000 nuclei across adult human brain. C_LIO_LIChromatin state annotation of >500,000 candidate cis-regulatory elements distinguishes active enhancers from accessible and Polycomb-repressed regions. C_LIO_LICell-type-resolved regulatory networks and sequence-based deep learning model prioritize functional neuropsychiatric risk variants. C_LIO_LISpatial epigenomic imputation reveals laminar layer-specific Polycomb repression programs. C_LIO_LIIntegration with 3D genome architecture reveals neuron-specific super long-range chromatin loops silencing early developmental genes. C_LIO_LIEvolutionary analysis uncovers conserved active regulatory grammar but divergent repressive landscape. C_LI

genomics↗

bioRxiv2026

Neural representations of dynamic social interactions

Humans readily infer others attributes and their complex web of social relationships from everyday social interactions. Yet, the neural mechanisms that transform these transient interactions into structured, multidimensional social knowledge remain unknown. Here, using a naturalistic fMRI paradigm, we develop a computational framework demonstrating how the human brain factorizes and integrates dynamic social interactions to construct multiplex social knowledge. This approach not only predicts neural responses during movie-viewing, but also enables the reconstruction of subjective social cognitive maps directly from brain activity. Crucially, the relational geometry of these reconstructed maps accurately predicts inferred personality traits, suggesting that relational and trait knowledge emerge from a shared neural representation reflecting interactional dynamics. Together, these findings provide a unifying computational framework for how the brain constructs multiplex social knowledge from observing naturalistic social interactions over time.

neuroscience↗

bioRxiv2026

An Integrated Single-Cell and Epigenomic Resource for Comparative Analysis of the Basal Ganglia

The basal ganglia regulate motor, cognitive, and affective behaviors, and their dysfunction underlies diverse neurological and psychiatric disorders. Comprehensive, accessible multi-omics resources are needed to understand the regulatory mechanisms governing basal ganglia cell types. Here we present an open, interactive web-based platform for exploring single-cell multi-omics datasets from basal ganglia, generated using 10X Multiome, snm3C-seq, and Paired-Tag technologies from the BICAN (NIH BRAIN Initiative Cell Atlas Network) consortium. The platform is available at https://basalganglia.epigenomes.net/ and enables integrated visualization of gene expression, chromatin accessibility, DNA methylation, histone modifications, and chromatin conformation across cell types and human, macaque, marmoset, and mouse species, with direct genome browser support and comparative epigenomic functionality. Representative analyses demonstrate cell-type-specific regulatory landscapes, conserved and species-specific regulatory elements, and links between epigenomic regulation and transcription. This resource provides a scalable, community-oriented foundation for advancing basal ganglia biology and interpreting regulatory mechanisms relevant to brain function and disease. HighlightsO_LIIntegrated single-cell epigenomic resource for basal ganglia C_LIO_LIInteractive genome browser enables multi-omics and cross-species exploration C_LIO_LIReveals cell-type-specific and species-specific regulatory landscapes C_LIO_LISupports community access to complex brain epigenomic datasets C_LI

genomics↗