Biology subjects

Fang, Q.

Publications and source records attributed to Fang, Q..

At least 19 recordsLinked to original sources

bioRxiv2026

An integrated data exploration engine of knowledge, expression and genetic association for human transposable elements

Transposable elements (TEs) constitute a substantial fraction of the human genome and contribute to genomic and epigenomic regulation. However, TE-related knowledge remains fragmented across the literature and databases, with inconsistent identifiers hindering integration and reuse. Here, we present TE-Dee (Transposable Element Data Exploration Engine), a curated resource that harmonizes literature-derived TE relationships with TE annotations, tissue-specific expression, and GTEx v11 eQTL associations. TE-Dee contains 10,387 entities and 9,583 curated relationships from 2,308 publications, 1,505 leaf-level TE classification records, and 11,334,060 instance-level observations generated by intersecting 640,456 reference TE intervals with significant variant-gene associations across 50 GTEx tissue categories. By linking molecular knowledge to genomic, transcriptomic and genetic evidence, TE-Dee provides reusable data for investigating TE biology, gene-regulatory and disease-related mechanisms, and a structured corpus for training and benchmarking data-driven and artificial intelligence models. TE-Dee is available at https://bis.zju.edu.cn/tedee/.

bioinformatics↗

bioRxiv2026

Using large language models for enhancing accessibility for Monte Carlo photon transport simulations and beyond

SignificanceComputational modeling and the use of simulation software tools are essential for biomedical optics research. Designing effective simulations often requires in-depth understanding of the underlying physical problems and proper configuration of the software settings, which often constitute key barriers for novice users including students. The rapid emergence of large language models (LLMs) offers new opportunities for natural-language-based interaction, but integrating them with technical software remains challenging because of their limited output reproducibility. Overcoming these limitations would allow more intuitive, efficient, and reproducible interaction between scientists and scientific software. AimWe investigate the use of LLMs in quantitative biophotonics simulation tools, with a goal of enabling novice users to build complex photon simulations using intuitive natural-language-based problem descriptions. ApproachWe have explored prompt engineering strategies that enable LLMs to bridge the gap between natural language descriptions and advanced simulation software by constraining LLM outputs using a data schema (i.e., format) and a modular component architecture, followed by deterministic validation to ensure correctness and reproducibility of the outputs. ResultsUsing Monte Carlo eXtreme (MCX) - a widely used photon transport simulator - as an example, we showcase the capability of the proposed framework to convert user descriptions to structured simulation inputs. Benchmarked using 33 diverse natural language simulation descriptions, our LLM interface, MCX-LLM, achieves 98% accuracy and 99% repeatability, with an average processing time of 8.96 seconds per prompt. The framework also successfully handles various linguistic styles and diverse simulation settings, achieving a 100% success rate on 20 unconstrained real-world prompts. With only minor adjustments, our LLM interface also produces valid inputs for a finite-element-based diffusion solver to demonstrate generality towards other optical simulators. ConclusionsBy combining LLMs capability for textual data comprehension with structured constraints, this work provides a pathway to making complex scientific tools accessible while ensuring the reliability and technical correctness required for rigorous scientific research. MCX-LLM has been integrated with MCX Cloud accessible at https://mcx.space/cloud.

bioengineering↗

bioRxiv2026

Regulatory co-option of a homeobox gene drives parasitoid venom evolution

How gene regulatory networks are rewired to generate phenotypic and functional innovation remains a central question in evolutionary biology. Parasitoid wasp venoms provide a powerful system for addressing this question, as their repertoires evolve rapidly through extensive lineage-specific turnover, yet the regulatory principles underlying such flexibility are largely unknown. Here we integrate tissue-resolved transcriptomic, chromatin-accessibility and histone-modification profiling to reconstruct the venom regulatory network of the parasitoid wasp Pteromalus puparum. We show that venom expression is embedded in distinct chromatin states and shaped by regulatory elements associated with venom-gland transcription. Comparative and functional analyses support a general model in which regulators related to the endoplasmic reticulum stress and unfolded protein response pathways have been repeatedly recruited to venom regulation across venomous lineages. Unexpectedly, we identify the recently co-opted homeobox gene Lbx as a lineage-specific hub that regulates more than half of venom genes and is linked to enhancer evolution. These results reveal a nested model of venom regulatory evolution, in which an ancestral secretory programme provides a reusable regulatory backbone, while newly co-opted homeobox gene specify a lineage-specific venom expression. Our study highlights regulatory co-option as a mechanism by which conserved developmental genes can acquire new physiological functions during adaptive evolution.

evolutionary biology↗

bioRxiv2026

NeuroCaptain v2 - Interactive Three-Dimensional fNIRS Optode and Probe Montage Design Platform Based on Blender

SignificanceAccurate and reproducible optode placement is crucial for obtaining high-quality fNIRS data in both individual and group-level neuroimaging studies. Conventional optode/probe montage design tools usually transform a probe layout defined in 2D Cartesian space onto a 3D head surface using a mass-spring model. Such mechanical transformation, combined with the indirect mapping between the 2D probe definition and the 3D target space, can introduce placement variations across different head surfaces and subjects. AimWe introduce NeuroCaptain v2, an open-source Blender-based add-on designed to enable interactive, anatomically guided optode design, registration, and cortical sensitivity visualization for fNIRS head-cap and probe creation. ApproachNeuroCaptain v2 enables researchers to add, move, and edit fNIRS sources and detectors directly over a 3D head surface mesh, defining anchored optode positions, as well as setting the stiffness of the springs between adjacent optodes. It then utilizes Blenders built-in physical simulation engine to relax the initial probe layout to satisfy the mechanical constraints. With the built-in mesh-based Monte Carlo (MMC) and diffusion-solver Redbird, NeuroCaptain v2 computes and renders 3D sensitivity maps to guide iterative optode adjustment. The resulting 3D optode layout is stored in the form of barycentric coordinates defined in a 10-20 landmark mesh, enabling consistent probe transfer across different head models. ResultsWe demonstrate interactive 3D montage design, cross-head-atlas probe registration, and cortical sensitivity visualization across multiple head geometries. Registering a probe across seven neurodevelopmental head atlases, the proposed anatomical-coordinate approach yields a mean per-optode standard deviation of 2.29 mm, a roughly 74% reduction in cross-subject placement variability compared to 8.68 mm using a conventional 2D-to-3D registration. ConclusionsNeuroCaptain v2 provides a reproducible, fully open-source workflow for fNIRS probe montage design that facilitates anatomically guided probe development and cross-subject registration directly in a three-dimensional anatomical environment.

neuroscience↗

bioRxiv2026

BRCA1 promotes homologous recombination through separable DNA and RAD51 binding activities within its disordered region.

The breast and ovarian tumor suppressor BRCA1 heterodimerizes with BARD1 to promote DNA double-strand break repair by homologous recombination (HR) and to protect stressed DNA replication forks against nuclease attack. The large, intrinsically disordered central region of BRCA1 harbors binding sites for DNA and multiple repair factors, but its lack of stable structure has hindered mechanistic dissection of these activities. Using biochemical mapping and NMR spectroscopy, we delineate the DNA binding and RAD51 interaction interfaces within this region and construct separation-of-function mutants that selectively ablate each activity. Both DNA binding and RAD51 interaction are required for BRCA1-BARD1 to promote RAD51-mediated DNA strand invasion, and DNA binding also contributes to BLM-DNA2 end resection. These findings provide mechanistic insights into how individual ligand binding activities within BRCA1 contribute to genome maintenance.

biochemistry↗

bioRxiv2026

EIF3H Sustains Translational Programs Essential for Proliferation in Human Primed Pluripotency

Pluripotent stem cells (PSCs) have remarkable capacity for unlimited self-renewal and differentiation into all somatic lineages. Although translational regulation has been implicated in the maintenance of PSC identity, the specific mechanisms involved remain poorly understood. Here, we identified EIF3H, a conserved subunit of the eIF3 translation initiation complex, as an essential regulator of human primed PSC proliferation and differentiation. CRISPR interference-mediated knockdown of EIF3H markedly reduced colony size, impaired proliferation, and diminished differentiation potential in all three germ layers. Integrated transcriptomic and translatomic profiling revealed that EIF3H loss decreased the translation of metal ion-related genes. Notably, the targeted suppression of metallothionein genes encoding metal-binding proteins recapitulated the proliferative defects observed in EIF3H-deficient PSCs, demonstrating a functional requirement for EIF3H-mediated translation of this gene family. Taken together, these findings establish EIF3H as a critical translational regulator that sustains PSC self-renewal and differentiation by maintaining the expression of key metabolic and stress-response genes, providing new insights into the molecular basis of pluripotency.

cell biology↗

bioRxiv2025

Chronic stress abnormalize microglial-vascular interaction via AT1R signaling and microglia activation to drive depression-like behaviors

Depression entails a range of pathological processes in the brain, typically characterized by microglia activation, neural dysfunction, and vascular dysregulation. While it is well established that activated microglia inflict damage to neurons through direct and indirect microglia-neuron interactions, their interaction with vasculature and the associated regulation of vascular structure and function in depression remain poorly understood. Here, using a mouse model of depression induced by chronic unpredictable stress (CUS), we find that in stressed mice, activated microglia present reduced motility and decreased contact area with vasculature, which is accompanied by pathological vascular structure and function, marked by reduced vessel density, narrowed vascular diameters, and sluggish blood flow velocity. We observe that vascular structure in the stressed mice is rapidly modified by the vascular-contacted microglia. These vascular-contacted microglia show upregulated angiotensin II type 1 receptor (AT1R) expression, which is not present in the vascular-uncontacted microglia. Furthermore, we demonstrate that AT1R signaling together with microglia activation under chronic stress are critical mediators for the altered microglial-vascular contact situation, vascular dysregulation, as well as the depression-like behaviors. Together, our findings reveal that under CUS, the aberrant microglial-vascular interaction, including the dysregulated microglial vasoregulation arising from AT1R signaling and microglia activation, leads to depression, forging a new link between chronic stress and depression.

neuroscience↗

bioRxiv2025

Improving neuroimaging headgear placement robustness using facial-landmark guided augmented reality

SignificanceAccurate and consistent probe placement is crucial in functional near-infrared spectroscopy (fNIRS) and electroencephalogram (EEG) experiments, especially in longitudinal and group-based studies. Both operator experience and subject head shape variability can affect placement accuracy. AimWe aim to develop an easy-to-use software, NeuroNavigatAR (NNAR), utilizing augmented reality (AR) and machine-learning to estimate and display in real-time the subjects cranial and head landmarks to guide consistent headgear placement. ApproachBy applying a facial recognition toolbox to the image frames extracted from a video camera, we can obtain and continuously track subject-specific three-dimensional (3-D) facial landmarks. Separately, we have precomputed a robust linear transformation between facial landmarks and key cranial landmarks, including nasion and preauricular points, using a large public head-model library consisting of over 1,000 subjects. These allow us to rapidly estmate subject-specific cranial landmarks and subsequently render atlas-derived head landmarks to the subjects camera stream. ResultsAn open-source graphical user interface implementing this AR system has achieved a speed of 15 frameper-second using a laptop. A median 10-20 position error of 1.52 cm was found when using a general adult atlas, and is further reduced to 1.33 cm and 0.75 cm when using age-matched atlas models and subject-specific head surfaces, respectively. NNAR demonstrated consistent head-landmark prediction errors across repeated measurement sessions; there is also no statistically significant difference in accuracy across age groups. ConclusionsNNAR is an easy-to-use AR headgear placement monitoring tool that is expected to significantly enhance consistency and reduce setup time for fNIRS and EEG probe donning across a wide range of studies.

neuroscience↗

bioRxiv2025

Targeting nucleolin facilitates the development of blood-tumor barrier-penetrating and glioblastoma-specific PROTACs

Targeted therapy for glioblastoma (GBM) is challenged by the blood-tumor barrier (BTB). Extracellular vesicles (EVs) from GBM cells play a role in transforming BBB into BTB, although the mechanisms are not fully understood. This study identifies nucleolin (NCL), a nucleomembrane shuttling protein, as being transferred from GBM cells to the surface of brain capillary endothelial cells, facilitating BTB formation. The aptamer AS1411, which targets NCL, is shown to cross the BTB via receptor-mediated transcytosis (RMT) and selectively recognize GBM cells in an NCL-dependent manner. Beyond its targeting capabilities, AS1411 has been repurposed to recruit the E3 ligase MDM2 in PROTACs, leveraging the intracellular interaction of NCL with MDM2. Utilizing AS1411s multifunctionality in BTB penetration, GBM cell targeting, and MDM2 recruitment, we conjugated AS1411 to VEGFR2 or EGFR ligands to create PROTAC degraders. These constructs induce NCL- and MDM2-dependent ubiquitination and degradation of VEGFR2 or EGFR, demonstrating significant anti-GBM efficacy both in vitro and in vivo, with no toxicity to normal cells. Overall, NCL from GBM-derived EVs emerges as a crucial mediator of BTB formation and serves as a receptor for AS1411-mediated RMT, paving the way for developing PROTACs that effectively traverse BTB and target GBM. GRAPHICAL ABSTRACTS O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/666084v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@79778org.highwire.dtl.DTLVardef@6984d8org.highwire.dtl.DTLVardef@1909eddorg.highwire.dtl.DTLVardef@1adf342_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

AWmeta empowers adaptively-weighted transcriptomic meta-analysis

Transcriptomic meta-analysis enhances biological veracity and reproducibility by integrating diverse studies, yet prevailing P-value or effect-size integration approaches exhibit limited power to resolve subtle signatures. We present AWmeta, an adaptively-weighted framework that unifies both paradigms. Benchmarking across 35 Parkinsons and Crohns disease datasets spanning diverse tissues and adaptively down-weighting underpowered studies, AWmeta yields higher-fidelity differentially expressed genes (DEGs) with markedly reduced false positives and establishes superior gene differential quantification convergence at both gene and study levels over state-of-the-art random-effects model (REM) and original studies. AWmeta requires fewer samples and DEGs from original studies to achieve substantial gene differential estimates, lowering experimental costs. We demonstrate AWmetas remarkable stability and robustness against external and internal perturbations. Crucially, AWmeta prioritizes disease tissue-specific mechanisms with higher functional coherence than those from REM and original studies. By bridging statistical rigor with mechanistic interpretability, AWmeta harmonizes heterogeneous transcriptomic data into actionable insights, serving as a transformative tool for precision transcriptomic integration.

bioinformatics↗

bioRxiv2025

Mitochondrial translation termination, recycling, reinitiation, and rescue for in-frame and out-of-frame contexts

Because mitochondria diverged from a bacterial ancestor during evolution, the mitochondrial protein synthesis system includes both mRNAs and translation factors with unique characteristics. However, the molecular mechanisms underlying translation termination, recycling, and quality control remain unclear. Here, via high-resolution mitochondrial Ribo-Seq and Disome-Seq, we revealed: the specificity of release factors for different kinds of stop codons; the role of mtRF1 in vertebrates, which do not have noncanonical stop codons in their main ORFs; the recycling-coupled translation of internal ORFs; and the rescue of mitoribosomes in the early elongation stage. mtRF1L is a universal release factor that recognizes all stop codons, whereas mtRF1 recognizes only AGA/AGG noncanonical stop codons. Additionally, mtRF1 terminates the translation of out-of-frame ORFs that end with AGA/AGG. We also found that mtRRF and mtIF3 are required for mitoribosome recycling on stop codons and for the reinitiation of internal ORF translation. Mitoribosomes that stall at start codons are major substrates of the rescue factors ICT1, mtRF-R, and mtRES1. Moreover, HEMK1-mediated methylation of release factors enhances the termination reaction on stop codons. Our results provide insights into the mitoribosome dynamics that are associated with the completion of protein synthesis.

molecular biology↗

bioRxiv2025

Stroke Shifts Brain Dynamics Toward Criticality: Evidence from Intrinsic Neural Timescales

Stroke disrupts brain function beyond focal lesions, altering multiscale temporal dynamics essential for information processing. We investigated intrinsic neural timescales (INT) and other properties of long-range temporal correlations, using longitudinal fMRI data from 15 ischemic stroke patients across six months, and compared them to age-matched controls. Results show that stroke patients exhibited significantly prolonged INT in multiple cortical regions, reflecting slowed temporal dynamics and disrupted hierarchy. These dynamic changes persisted through recovery and were more pronounced in patients with poor outcomes, especially within cognitive control networks. Computational modelling suggested that stroke-induced INT prolongation driven by heightened neuronal excitability reflects a dynamic shift towards criticality. Our findings position long-range temporal correlations and INT as potential biomarkers for monitoring and predicting functional recovery. This framework provides a novel perspective on stroke-induced brain changes and suggests avenues for targeted neurorehabilitation using interventions aiming at restoring intrinsic temporal dynamics.

neuroscience↗

bioRxiv2025

SNARE complex assembly and disassembly dynamics in response to Ca2+ current activation in live cells

A SNAP25 based FRET construct named SCORE (SNARE COmplex REporter) has revealed a transient FRET increase that specifically occurred at fusion sites preceding fusion events by tens of milliseconds and presumably reflects vesicle priming. The FRET increase lasts for a few seconds until it is reversed. In those experiments, the FRET increase was found to be localized to areas <0.5 {micro}m2 at sites of transmitter release as detected amperometrically using electrochemical detector arrays. Due to the localization to such small areas, it was unknown if the reversal of the FRET increase is due to local dispersion of high-FRET SCORE copies leaving the site after fusion and exchange with surrounding low-FRET copies, or if it reflects disassembly of the high-FRET complexes. To resolve this question, we performed whole-cell patch clamp pulse stimulation experiments, imaging the entire footprint of the cells in Total Internal Reflection Fluorescence (TIRF) excitation mode such that diffusional exchange between high-FRET and low-FRET copies does not produce a net FRET change. We show here that pulse stimulation of calcium currents results in FRET ratio transients with a time course very similar that related to fusion events. By comparing the kinetics of the FRET ratio decay with analytical and numerical diffusion simulation results, we show that the experimentally observed kinetics cannot be explained by diffusional exchange and conclude that the SCORE FRET ratio transients reflect incorporation of SCORE in SNARE complexes followed by SNARE complex disassembly. Experiments using Synaptobrevin 2/Cellubrevin double knock-out mouse embryonal chromaffin cells showed no pulse induced FRET change, indicating that the vSNARE is required for the incorporation of SCORE (or SNAP25 in wild type cells) in the SNARE complex during priming. Statement of SignificanceIn chromaffin cells, SNAP25-based FRET constructs (SCORE) revealed transient FRET increases within <0.5 {micro}m2 areas, preceding individual fusion events that reversed within seconds. It remained unknown whether this reversal stems from high-FRET complex disassembly or diffusion-mediated exchange with low-FRET complexes. Here, we performed whole-cell patch-clamp pulse stimulation with TIRF microscopy, imaging large [~]30 {micro}m2 areas of the cell footprint. Calcium currents induced FRET transients with the same decay time constant of [~]1.5 s, significantly shorter than the time scale of diffusion. The SCORE FRET ratio thus reports in real time the dynamics of SNRE complex assembly and disassembly in live cells. Using Synaptobrevin 2/Cellubrevin double knock-out mouse chromaffin cells we show that vSNAREs are required for SNAP25 incorporation into SNARE complexes during priming.

biophysics↗

bioRxiv2025

Gating of hair cell Ca2+ channels governs the activity of cochlear neurons

Our sense of hearing processes sound intensities spanning six orders of magnitude. In the ear, postsynaptic spiral ganglion neurons (SGNs) tile this intensity range with their firing rate codes. Presynaptic inner hair cells (IHCs) vary Ca2+-influx among their active zones (AZs) diversifying glutamate release and likely contributing to SGN firing diversity. Here we show that low-voltage activation of IHC-Ca2+-influx of mice, modeling the human CaV1.3A749G mutation, increases spontaneous SGN-firing and lowers sound threshold. Altered synaptic morphology in CaV1.3A749G/A749G mice already at ambient sound levels of standard mouse husbandry indicates a risk for noise-induced alterations in CaV1.3A749G patients. We conclude that heterogeneous voltage-dependence of CaV1.3 activation among IHC-AZs contributes to the diversity of SGN firing for sound intensity coding and synaptic vulnerability.

neuroscience↗

bioRxiv2024

Creating anatomically-derived, standardized, customizable, and three-dimensional printable head caps for functional neuroimaging

AbstractO_ST_ABSSignificanceC_ST_ABSConsistent and accurate probe placement is a crucial step towards enhancing the reproducibility of longitudinal and group-based functional neuroimaging studies. While the selection of headgear is central to these efforts, there does not currently exist a standardized design that can accommodate diverse probe configurations and experimental procedures. AimWe aim to provide the community with an open-source software pipeline for conveniently creating low-cost, 3-D printable neuroimaging head caps with anatomically significant landmarks integrated into the structure of the cap. ApproachWe utilize our advanced 3-D head mesh generation toolbox and 10-20 head landmark calculations to quickly convert a subjects anatomical scan or an atlas into a 3-D printable head cap model. The 3-D modeling environment of the open-source Blender platform permits advanced mesh processing features to customize the cap. The design process is streamlined into a Blender add-on named "NeuroCaptain". ResultsUsing the intuitive user interface, we create various head cap models using brain atlases, and share those with the community. The resulting mesh-based head cap designs are readily 3-D printable using off-the-shelf printers and filaments while accurately preserving the head topology and landmarks. ConclusionsThe methods developed in this work result in a widely accessible tool for community members to design, customize and fabricate caps that incorporate anatomically derived landmarks. This not only permits person-alized head cap designs to achieve improved accuracy, but also offers an open platform for the community to propose standardizable head caps to facilitate multi-centered data collection and sharing.

neuroscience↗

bioRxiv2024

Revisiting equivalent optical properties for cerebrospinal fluid to improve diffusion-based modeling accuracy in the brain

SignificanceThe diffusion approximation (DA) is used in functional near-infrared spectroscopy (fNIRS) studies despite its known limitations due to the presence of cerebrospinal fluid (CSF). Many of these studies rely on a set of empirical CSF optical properties, recommended by a previous simulation study, that were not selected for the purpose of minimizing DA modeling errors. AimWe aim to directly quantify the accuracy of DA solutions in brain models by comparing those with the gold-standard solutions produced by the mesh-based Monte Carlo (MMC), based on which we derive updated recommen-dations. ApproachFor both a 5-layer head and Colin27 atlas models, we obtain DA solutions by independently sweeping the CSF absorption ({micro}a) and reduced scattering [Formula] coefficients. Using an MMC solution with literature CSF optical properties as reference, we compute the errors for surface fluence, total brain sensitivity and brain energy-deposition, and identify the optimized settings where the such error is minimized. ResultsOur results suggest that previously recommended CSF properties can cause significant errors (8.7% to 52%) in multiple tested metrics. By simultaneously sweeping {micro}a and [Formula],we can identify infinite numbers of solutions that can exactly match DA with MMC solutions for any single tested metric. Furthermore, it is also possible to simul-taneously minimize multiple metrics at multiple source/detector separations, leading to our new recommendation of setting [Formula] while maintaining physiological {micro}a for CSF in DA simulations. ConclusionOur new recommendation of CSF equivalent optical properties can greatly reduce the model mismatches between DA and MMC solutions at multiple metrics without sacrificing computational speed. We also show that it is possible to eliminate such a mismatch for a single or a pair of metrics of interest.

neuroscience↗

bioRxiv2024

Three-dimension transcriptomics maps of whole mouse embryo during organogenesis

Understanding mammalian development heavily relies on classical animal models like the house mouse (Mus musculus). Advanced spatial transcriptomics has enabled biologists to break new ground in studies of molecular dynamics and cellular patterning during embryonic development with spatiotemporal resolution. To construct a comprehensive developmental trajectory, current three-dimensional (3D) spatial transcriptomic profiling leverages mouse embryos from gastrulation (E5.5) to organogenesis (E13.5) in continuity. However, a crucial phase for early organogenesis between E9.5 and E11.5 was deficient. To unveil the mystery of this stage, we present the 3D transcriptomics of mouse embryos at E9.5 and E11.5, with a widely applicable reconstruction workflow that bypasses sophisticated bioinformatic calculations. As our 3D atlas is generated at single-cell resolution, we demonstrate how organogenetic processes can be interpreted at different levels of granularity, from local cellular interactions to whole embryonic regionalization. We release the open-access database MOSTA3D (Mouse Organogenesis Spatiotemporal Transcriptomic Atlas in Three-dimensional) and hope a broader community will contribute to extending this framework from conception to senility in the near future.

developmental biology↗

bioRxiv2024

Engineering Microglial Cells to Promote Spinal Cord Injury Recovery

Spinal cord injury (SCI) can result in irreversible damage, leading to lifelong paralysis for affected individuals. Microglias dual impact on neuronal regeneration after SCI, driven by their distinct roles at different stages, merits further study. We conducted a bioinformatic analysis of single-cell transcriptomes (scRNA), spatial transcriptomic (ST) data, and bulk RNA-seq data from Gene Expression Omnibus (GEO) datasets. The data were processed using R packages such as "Seurat", "DESeq2","limma" and "GSVA." Additionally, we utilized Gene Set Enrichment Analysis (GSEA) and the Enrichr web servers. Analysis of single-cell data and spatial transcriptomics has revealed notable changes in the microglial cell landscape in SCI. These changes encompass the inhibition of innate microglial cells, while reactive microglial cells exhibit pronounced reactive hyperplasia. Moreover, the TGF{beta} signaling pathway plays a crucial role in regulating the migration of innate microglial cells to enhance SCI recovery. However, reactive microglial cells exhibiting high Trem2 expression contribute to the neuroinflammatory response and can effectively modulate neural cell death in SCI. In particular, inhibiting Trem2 in reactive microglial cells not only reduces inflammation but also mitigates spinal cord injury, and enhancing the TGF{beta} signaling pathway. Whats more, the use of iPSC-derived microglial cells, which have demonstrated their capacity to augment the potential for replacing the functions of naive microglial cells, iPSC-derived microglia have the potential to replace the functions of naive microglial cells, holds significant promise in addressing SCI. Therefore, we posit that the engineering of microglial cells to promote the SCI recovery. The approach of inhibiting Trem2-mediated neuroinflammatory responses and transplanting iPSC-derived microglia with long-term TGF{beta} stimulation may offer potential improvements in SCI recovery.

neuroscience↗