Biology subjects

Lai, Y.

Publications and source records attributed to Lai, Y..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Leg choice for volitional goal-directed stepping is primarily influenced by effort rather than success: A preliminary investigation in neurotypical adults

During reaching, arm choice depends on success and motor effort. Whether these factors influence leg choice for stepping behavior is unknown. Here, we conducted two experiments (1: proof-of-principle; 2: kinematic analysis) to explore whether limb selection for goal-directed stepping depends on success and/or effort under two Choice conditions: Free (choose either leg) and Constrained (no choice - only left leg). For both experiments, in which Free trials always preceded Constrained trials, we adapted the classic center-out target array in which right-leg dominant neurotypical adults stood in the middle of the array and stepped to pre-cued targets as accurately as possible. The Free condition reflected the preferred limb choice. We compared success, effort, and self-perceived difficulty between Free and Constrained trials, separately for three (Experiment 1) and two (Experiment 2) regions. Overall, in Free condition, participants uniformly selected the limb ipsilateral to lateral left and right targets and with slight leg dominance-based bias for central targets. Success (step accuracy and consistency/precision) did not depend on Choice condition, rather, performance improved over repeated trials. Effort (peak vertical foot lift and step path ratio) depended on Choice condition. Finally, independent of Choice condition, participants perceived posterior targets (particularly far targets) as the most difficult during non-dominant left steps. Present findings suggest that effort may influence leg choice to a greater degree than success for goal-directed stepping. Future work that probes these findings robustness in patients with unilateral paresis (intrinsic constraint) may advance our understanding of the motor decision processes for goal-directed mobility behaviors.

neuroscience↗

bioRxiv2024

Virological characteristics of SARS-CoV-2 Omicron BA.5.2.48

With the prevalence of sequentially-emerged sublineages including BA.1, BA.2 and BA.5, SARS-CoV-2 Omicron infection has transformed into a regional epidemic disease. As a sublineage of BA.5, the BA.5.2.48 outbreak and evolved into multi-subvariants in China without clearly established virological characteristics, especially the pathogenicity. Though reduced airborne transmission and pathogenicity of former Omicron sublineages have been revealed in animal models, the virological characteristics of BA.5.2.48 was unidentified. Here, we evaluated the in vitro and in vivo virological characteristics of two isolates of the prevalent BA.5.2.48 subvariant, DY.2 and DY.1.1 (a subvariant of DY.1). DY.2 replicates more efficiently than DY.1.1 in HelahACE2+ cells and Calu-3 cells. The A570S mutation (of DY.1) in a normal BA.5 spike protein (DY.2) leads to a 20% improvement in the hACE2 binding affinity, which is slightly reduced by a further K147E mutation (of DY.1.1). Compared to the normal BA.5 spike, the double-mutated protein demonstrates efficient cleavage and reduced fusogenicity. BA.5.2.48 demonstrated enhanced airborne transmission capacity in hamsters than BA.2. The pathogenicity of BA.5.2.48 is greater than BA.2, as revealed in K18-hACE2 rodents. Under immune selection pressure, DY.1.1 shows stronger fitness than DY.2 in hamster turbinates. Thus the outbreaking prevalent BA.5.2.48 multisubvariants exhibites divergent virological features. ImportanceOmicron continues to circulate and evolves novel sublineages with indistinguishable pathogenicity and transmission. Therefore humanized Omicron-sensitive animal models must be applied to evaluate the virological characteritics and antiviral therapeutics. By using multiple models including the Omicron-lethal H11-K18-hACE2 rodents, BA.5.2.48 revealed higher pathogenicity in the novel H11-K18-hACE2 rodent models than the previously epidemic BA.2, and thus the models are more adapted to Omicron studies. Moreover, the regional outbreaking of BA.5.2.48 promotes the multidirectional evolution of its subvariants, gaining either enhanced pathogenicity or a fitness in upper airways which is associated with higher transmission, highlighting the importance of surveillance and virological studies on regionally endemic sublineages which represents the short-run evolutionary direction of Omicron.

microbiology↗

bioRxiv2024

Characterization of the SARS-CoV-2 BA.5 Variants in H11-K18-hACE2 Hamsters

This study aims to comprehensively characterize the SARS-CoV-2 BA.5 variants using K18 hACE2 transgenic mice and golden hamsters as model organisms. Previous research on SARS-CoV-2 has utilized both mouse and hamster models, leading to conflicting results concerning the viruss lethality. In our study, the finding suggests that H11-K18 hACE2 golden hamsters closely mimic the disease progression observed in human COVID-19 cases caused by BA.5 variants, demonstrating consistent severity and symptoms comparable to severe infections. Additionally, hamsters exhibit heightened respiratory viral replication, accurately reflecting the clinical viral kinetics observed in humans. The study emphasizes the critical importance of selecting an appropriate animal model for SARS-CoV-2 research, while also providing robust support for the hypothesis that BA.5 variants contribute to fatal outcomes in COVID-19 cases. These findings highlight the pivotal role of the golden hamster model in advancing our understanding of the pathogenic mechanisms underlying SARS-CoV-2 variants, as well as in the development of targeted therapeutic strategies. Significance StatementOur research work explores groundbreaking insights that could reshape our understanding of COVID-19 and pave the way for targeted therapies. We use golden hamster models to express the possibility of different animal models could contribute to human diseases. We hope this finding could clarify some conflicts existed, and help further development of medication for COVID.

immunology↗

bioRxiv2024

IOBR2: Multidimensional Decoding Tumor Microenvironment for Immuno-Oncology Research

The use of large transcriptome datasets has greatly improved our understanding of the tumor microenvironment (TME) and helped develop precise immunotherapies. The increasing popularity of multi-omics sequencing, single-cell transcriptome sequencing (scRNA), and spatial transcriptome sequencing has led to numerous new discoveries. However, these findings require clinical phenotypic validation with a large sample size. To enhance the integration of multi-omics in advancing research on the tumor microenvironment, we have developed a systematic and comprehensive analytical tool (Immuno-Oncology Biological Research 2, IOBR2) based on our prior work. IOBR2 offers six modules for TME analysis based on multi-omics data. These modules cover data preprocessing, TME estimation, TME infiltrating patterns, cellular interactions, genome and TME interaction, and visualization for TME relevant features, as well as modelling based on key features. IOBR2 integrates multiple vital microenvironmental analysis algorithms and signature estimation methods, simplifying the analysis and downstream visualization of the TME. In addition to providing a quick and easy way to construct gene signatures from single-cell data, IOBR2 also provides a way to construct a reference matrix for TME deconvolution from single-cell RNAseq. The analysis pipeline and feature visualization are user-friendly and provide a comprehensive description of the complex TME, offering insights into tumor-immune interactions. A comprehensive gitbook (https://iobr.github.io/book/) is available with a user-friendly manual and complete analysis workflow for each module.

cancer biology↗

bioRxiv2023

Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. The need for relieving OA pain is paramount but inadequately addressed, partly due to limited understandings of how pain signaling regulates non-neural tissues. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNF to attenuate NF-{kappa}B activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression. NGFR deficiency hyper-activates NF-{kappa}B in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-{kappa}B activation. Together, this study uncovers a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.

cell biology↗

bioRxiv2023

Biotin rescues manganese-induced Parkinson's disease phenotypes and neurotoxicity

Occupational exposure to manganese (Mn) induces manganism and has been widely linked as a contributing environmental factor to Parkinsons disease (PD), featuring dramatic signature overlaps between the two in motor symptoms and clinical hallmarks. However, the molecular mechanism underlying such link remains elusive, and for combating PD, effective mechanism-based therapies are lacking. Here, we developed an adult Drosophila model of Mn toxicity to recapitulate key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosome and mitochondria. We performed global metabolomics on flies at an early stage of toxicity and identified metabolism of the B vitamin, biotin (vitamin B7), as a master pathway underpinning Mn toxicity with systemic, body-brain increases in Mn-treated groups compared to the controls. Using BtndRNAi mutant flies, we show that biotin depletion exacerbates Mn-induced neurotoxicity, parkinsonism, and mitochondrial dysfunction; while in Mn-exposed wild-type flies, biotin feeding dramatically ameliorates these pathophenotypes. We further show in human induced stem cells (iPSCs)- differentiated midbrain dopaminergic neurons that the supplemented biotin protects against Mn-induced neuronal loss, cytotoxicity, and mitochondrial dysregulation. Finally, human data profiling biotin-related proteins show for PD cases elevated circulating levels of biotin transporters but not of metabolic enzymes compared to healthy controls, suggesting humoral biotin transport as a key event involved in PD. Taken together, our findings identified compensatory biotin pathway as a convergent, systemic driver of Mn toxicity and parkinsonian pathology, providing new basis for devising effective countermeasures against manganism and PD. Significance StatementEnvironmental exposure to manganese (Mn) may increase the risk for Parkinsons disease (PD); however, the mechanistic basis linking the two remains unclear. Our adult fruit fly (Drosophila) model of Mn toxicity recapitulated key Parkinsons hallmarks in vivo spanning behavioral deficits, neuronal loss, and mitochondrial dysfunction. Metabolomics identified the biotin (vitamin B7) pathway as a key mediator, featuring systemic biotin increases in the flies. Rescue trials leveraging biotin-deficient flies, wild-type flies, and human iPSC-derived dopaminergic neurons determined biotin as a driver of manganism, with the parkinsonian phenotypes dramatically reversed through biotin supplementation. Our findings, in line with overexpressed circulating biotin transporters observed in PD patients, suggest compensatory biotin pathway as a key to untangle the Mn-PD link for combating neurodegenerative disease.

neuroscience↗

bioRxiv2023

coRIC map: a framework for the exploration of multifaceted subcellular RNA-binding proteins

The ability of RNA-binding proteins (RBPs) to form complexes with other biomolecules underpins a broad range of functions and remarkable structural properties. Understanding the precise spatiotemporal dynamics of RBPs and their interacting partners in the steady state and upon perturbation is key to deciphering these aspects. Here, we present the coRIC (compartmentalized RNA Interactome Capture) map, an experimental resource and analytical pipeline to study the subcellular dynamics of RBPs through multimodal dataset integration and machine learning. Using this approach, we have generated an atlas comprising 1,768 RBPs distributed in a broad panel of subcellular compartments and delineated their intermolecular and intercompartmental relationships. We have also defined the hierarchy of RBP-containing complexes at multiple scales across the cell, uncovering previously unknown functions of multiple RBPs. Furthermore, we have investigated the changes in RBP complex composition and subcellular distribution in response to C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRIC map provides a valuable new approach for defining the roles of RBPs in homeostasis and disease.

cell biology↗

bioRxiv2023

ISMI-VAE: A Deep Learning Model for Classifying Disease Cells Using Gene Expression and SNV Data

Various studies have linked several diseases, including cancer and Covid-19, to single nucleotide variations (SNV). Although scRNA-seq technology can provide SNV and gene expression data, few studies have integrated and analyzed these multimodal data. To address this issue, this paper introduces Interpretable Single-cell Multimodal Data Integration Based on Variational Autoencoder (ISMI-VAE). ISMI-VAE leverages latent variable models that utilize the characteristics of SNV and gene expression data to overcome high noise levels, and uses deep learning techniques to integrate multimodal information, map them to a low-dimensional space, and classify disease cells. Moreover, ISMI-VAE introduces an attention mechanism to reflect feature importance and analyze genetic features that could potentially cause disease. Experimental results on three cancer data sets and one Covid-19 data set demonstrate that ISMI-VAE surpasses the baseline method in terms of both effectiveness and interpretability, and can effectively identify disease-causing gene features.

bioinformatics↗

bioRxiv2023

A partial Drp1 knockout improves autophagy flux independent of mitochondrial function

Dynamin-related protein 1 (Drp1) is typically known for its role in mitochondrial fission. A partial inhibition of this protein has been reported to be protective in experimental models of neurodegenerative diseases. The protective mechanism has been attributed primarily to improved mitochondrial function. Herein, we provide evidence showing that a partial Drp1-knockout improves autophagy flux independent of mitochondria. First, we characterized in cell and animal models that at low non-toxic concentrations, manganese (Mn), which causes parkinsonian-like symptoms in humans, impaired autophagy flux but not mitochondrial function and morphology. Furthermore, nigral dopaminergic neurons were more sensitive than their neighbouring GABAergic counterparts. Second, in cells with a partial Drp1-knockdown and Drp1+/- mice, autophagy impairment induced by Mn was significantly attenuated. This study demonstrates that autophagy is a more vulnerable target than mitochondria to Mn toxicity. Furthermore, improving autophagy flux is a separate mechanism conferred by Drp1 inhibition independent of mitochondrial fission.

cell biology↗

bioRxiv2023

Single-cell transcriptomic landscape deciphers novel olfactory neuroblastoma subtypes and intratumoral heterogeneity

Olfactory neuroblastoma (ONB) is an uncommon malignant tumor known to originate from the olfactory epithelial. The complex tumor ecosystem of this pathology remained unclear. Here, we explored the cellular components with ONB tumors based on scRNA profiles of 96,325 single-cells derived from 10 tumors and 1 olfactory mucosa sample. We discovered 11 major cell types, including 6 immune cell, 3 stromal cell subtypes and epithelial cluster in the tumor microenvironment (TME), and identified 5 common expression programs from malignant epithelial cells. We analyzed subclusters of TME and the interactions among different cell types in the TME. An innovative three-classification of ONB was established via scRNA analysis. Markers for categorizing tumor samples into new subtypes were elucidated. Different responses towards certain chemotherapy regimens could be inferred according to the molecular features of three tumor types. Relative abundance of immunosuppressive TAMs indicated the benefits of immunotherapies targeting myeloid cells.

cancer biology↗

bioRxiv2022

Spateo: multidimensional spatiotemporal modeling of single-cell spatial transcriptomics

Cells do not live in a vacuum, but in a milieu defined by cell-cell communication that can be measured via emerging high-resolution spatial transcriptomics approaches. However, analytical tools that fully leverage such data for kinetic modeling remain lacking. Here we present Spateo (aristoteleo/spateo-release), a general framework for quantitative spatiotemporal modeling of single-cell resolution spatial transcriptomics. Spateo delivers novel methods for digitizing spatial layers/columns to identify spatially-polar genes, and develops a comprehensive framework of cell-cell interaction to reveal spatial effects of niche factors and cell type-specific ligand-receptor interactions. Furthermore, Spateo reconstructs 3D models of whole embryos, and performs 3D morphometric analyses. Lastly, Spateo introduces the concept of "morphometric vector field" of cell migrations, and integrates spatial differential geometry to unveil regulatory programs underlying various organogenesis patterns of Drosophila. Thus, Spateo enables the study of the ecology of organs at a molecular level in 3D space, beyond isolated single cells.

systems biology↗

bioRxiv2022

Efficient repair of human homozygous genetic mutation by CRISPR/Cas9 mediated interlocus gene conversion

DNA double-strand breaks (DSBs) induced by gene editing tools are primarily resolved either by non-homologous end joining (NHEJ) or homology-directed repair (HDR) using exogenous synthetic DNA templates. Repaired by error-prone NHEJ may lead to unexpected indels at the targeted site. In the case of most genetic disorders, HDR-mediated precise correction using an exogenous homologous sequence is ideal. However, the therapeutic application of HDR might be especially challenging given the requirement for the codelivery of exogenous DNA templates with toxicity into cells, and the low efficiency of HDR could also limit its clinical application. Here, we used hematopoietic stem cells (HSCs) with genetic mutations to cause {beta}-thalassemia in HBB coding regions and discovered that many cells are actually repaired by CRISPR/Cas9-mediated gene conversion (GC) independent of exogenous synthetic DNA templates. We show that pathogenic mutations in the HBB coding regions of HSCs can be repaired efficiently through CRISPR/GC using the paralog gene HBD as the internal template. Electroporations of Cas9 for ribonucleoprotein with sgRNA into haematopoietic stem and progenitor cells (HSPCs) with a variety of pathogenic gene mutations also resulted in effective conversion of mutations to normal wild-type sequences without exogenous DNA template. Moreover, the edited HSCs can repopulate the haematopoietic system and generate erythroid cells with a greatly reduced propensity for thalassemia after transplantations. Thus, CRISPR/GC, independent of exogenous DNA templates, holds great promise for gene therapy of genetic diseases.

genetics↗

bioRxiv2022

Screening of hydrocarbon-stapled peptides for inhibition of calcium-triggered exocytosis

The so-called primary interface between the SNARE complex and synaptotagmin-1 (Syt1) is essential for Ca2+-triggered neurotransmitter release in neuronal synapses. The interacting residues of the primary interface are conserved across different species for synaptotagmins (Syt1, Syt2, Syt9), SNAP-25, and syntaxin-1A homologs involved in fast synchronous release. This Ca2+-independent interface forms prior to Ca2+-triggering and plays a role in synaptic vesicle priming. This primary interface is also conserved in the fusion machinery that is responsible for mucin granule membrane fusion. Ca2+-stimulated mucin secretion is mediated by the SNAREs syntaxin-3, SNAP-23, VAMP8, synaptotagmin-2, and other proteins. Here, we designed and screened a series of hydrocarbon-stapled peptides consisting of SNAP-25 fragments that included some of the key residues involved in the primary interface as observed in high-resolution crystal structures. We selected a subset of four stapled peptides that were highly -helical as assessed by circular dichroism and that inhibited both Ca2+-independent and Ca2+-triggered ensemble lipid-mixing with neuronal SNAREs and Syt1. In a single-vesicle contentmixing assay with reconstituted neuronal SNAREs and synaptotagmin-1 or with reconstituted airway SNAREs and synaptotagmin-2, the selected peptides also suppressed Ca2+-triggered fusion. Taken together, hydrocarbon-stapled peptides that interfere with the primary interface consequently inhibit Ca2+-triggered exocytosis. Our inhibitor screen suggests that these compounds may be useful to combat mucus hypersecretion that is a major cause of airway obstruction in the pathophysiology of COPD, asthma and cystic fibrosis.

pharmacology and toxicology↗

bioRxiv2022

Ingestible capsule for detecting labile inflammatory biomarkers in situ

Transient molecules in the gastrointestinal (GI) tract, such as nitric oxide and hydrogen sulfide, are key signals and mediators of inflammatory bowel disease (IBD). Because these molecules are extremely short-lived in the body, they are difficult to detect. To track these reactive molecules in the GI tract, we have developed a miniaturized device that integrates genetically-engineered probiotic biosensors with a custom-designed photodetector and readout chip. Leveraging the molecular specificity of living sensors, we genetically encoded bacteria to respond to IBD-associated molecules by luminescing. Low-power electronic readout circuits (nanowatt power) integrated into the device convert the light from just 1 L of bacterial culture into a wireless signal. We demonstrate biosensor monitoring in the GI tract of small and large animal models and integration of all components into a sub-1.4 cm3 ingestible form factor capable of supporting wireless communication. The wireless detection of short-lived, disease-associated molecules could support earlier diagnosis of disease than is currently possible, more accurate tracking of disease progression, and more timely communication between patient and their care team supporting remote personalized care.

synthetic biology↗

bioRxiv2021

Cell transcriptomic atlas of the non-human primate Macaca fascicularis

Studying tissue composition and function in non-human primates (NHP) is crucial to understand the nature of our own species. Here, we present a large-scale single-cell and single-nucleus transcriptomic atlas encompassing over one million cells from 43 tissues from the adult NHP Macaca fascicularis. This dataset provides a vast, carefully annotated, resource to study a species phylogenetically close to humans. As proof of principle, we have reconstructed the cell-cell interaction networks driving Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases and intersected our data with human genetic disease orthologous coordinates to identify both expected and unexpected associations. Our Macaca fascicularis cell atlas constitutes an essential reference for future single-cell studies in human and NHP.

cell biology↗

bioRxiv2021

Cas9-Assisted Biological Containment of a Genetically Engineered Human Commensal Bacterium and Genetic Elements

Sophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Biosensing bacteria can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiring thyA via horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacterium Bacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination for at least 10 days. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.

synthetic biology↗

bioRxiv2021

Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in PSC.

ObjectiveConflicting microbiota data exist for primary sclerosing cholangitis (PSC) and experimental models. Goal: Define complex interactions between resident microbes and their association in PSC patients by studying antibiotic-treated specific pathogen-free (SPF) and germ-free (GF) multi-drug-resistant 2 deficient (mdr2-/-) mice. DesignWe measured weights, liver enzymes, RNA expression, histological, immunohistochemical and fibrotic biochemical parameters, fecal 16s rRNA gene profiling, and metabolomic endpoints in gnotobiotic and antibiotic-treated SPF mdr2-/- mice and targeted metagenomic analysis in PSC patients. ResultsGF mdr2-/- mice had exaggerated hepatic inflammation and fibrosis with 100% mortality by 8 weeks; early SPF autologous stool transplantation rescued liver-related mortality. Broad-spectrum antibiotics and vancomycin alone accelerated disease in weanling SPF mdr2-/- mice, indicating that vancomycin-sensitive resident microbiota protect against hepatobiliary disease. Vancomycin treatment selectively decreased Lachnospiraceae and short-chain fatty acids (SCFAs) but expanded Enterococcus and Enterobacteriaceae. Antibiotics increased cytolysin-expressing E. faecalis and E. coli liver translocation; colonization of gnotobiotic mdr2-/- mice with translocated E. faecalis and E. coli strains accelerated liver inflammation and mortality. Lachnospiraceae colonization of antibiotic pre-treated mdr2-/- mice reduced liver fibrosis, inflammation and translocation of pathobionts, while Lachnospiraceae-produced SCFA decreased fibrosis. Fecal E. faecalis/ Enterobacteriaceae was positively and Lachnospiraceae was negatively associated with PSC patients clinical severity Mayo risk scores. ConclusionsWe identified specific functionally protective and detrimental resident bacterial species in mdr2-/- mice and PSC patients with associated clinical outcomes. These insights may guide personalized targeted therapeutic interventions in PSC patients.

microbiology↗

bioRxiv2021

Spatiotemporal transcriptome at single-cell resolution reveals key radial glial cell population in axolotl telencephalon development and regeneration

Brain regeneration requires a precise coordination of complex responses in a time- and region-specific manner. Identifying key cell types and molecules that direct brain regeneration would provide potential targets for the advance of regenerative medicine. However, progress in the field has been hampered largely due to limited regeneration capacity of the mammalian brain and understanding of the regeneration process at both cellular and molecular level. Here, using axolotl brain with extrodinary regeneration ability upon injury, and the SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we reconstructed the first architecture of axolotl telencephalon with gene expression profiling at single-cell resolution, and fine cell dynamics maps throughout development and regeneration. Intriguingly, we discovered a marked heterogeneity of radial glial cell (RGC) types with distinct behaviors. Of note, one subtype of RGCs is activated since early regeneration stages and proliferates while other RGCs remain dormant. Such RGC subtype appears to be the major cell population involved in early wound healing response and gradually covers the injured area before presumably transformed into the lost neurons. Altogether, our work systematically decoded the complex cellular and molecular dynamics of axolotl telencephalon in development and regeneration, laying the foundation for studying the regulatory mechanism of brain regeneration in the future.

developmental biology↗