Biology subjects

Yao, H.

Publications and source records attributed to Yao, H..

At least 37 records · Page 2Linked to original sources

bioRxiv2026

Mouse behavioral genomics identifies Creld1 as a gatekeeper of somatosensation

Somatosensation enables the perception of touch, temperature, pain, and itch. These sensory modalities are mediated by primary sensory neurons in the dorsal root ganglion (DRG), which convert physical and chemical stimuli into electrical signals using specialized molecular sensors, including the touch sensor PIEZO2 (Ref1,2) and temperature sensors such as TRPV1 (Ref3,4), coupled with downstream voltage-gated sodium channels (Nav) like Nav1.7 (Ref5,6). However, the full repertoire of molecular components involved in somatosensory processing remains incompletely identified. Here, we developed an efficient postnatal CRISPR-Cas9 knockout platform to screen DRG-expressed genes via AAV9-sgRNA delivery. Combining this approach with behavioral assays of somatosensory responses, we validated the roles of PIEZO2 and TRPV1 in sensing gentle touch and noxious heat, respectively, and the broad involvement of Nav1.7 in distinct somatosensory modalities. Remarkably, a targeted screen of 20 DRG-expressed genes identified the Cysteine-rich with EGF-like domains 1 (Creld1) as a master regulator of somatosensation. Either sgRNA-mediated postnatal knockout or tamoxifen-induced Cre-mediated deletion of Creld1 in DRG neurons resulted in profound behavioral deficits in touch, temperature, pain, and itch perception, while its overexpression enhanced touch and thermal responses. Mechanistically, Creld1 functions as a novel auxiliary regulator of Nav for controlling the excitability of DRG neurons. The biochemical interaction and functional modulation of Nav by mouse Creld1 are mediated via its C-terminal transmembrane region. Notably, this domain is conserved in mouse Creld1 and some isoforms of human CRELD1, resulting in an isoform-dependent regulation of Nav1.7. Together, this work establishes a robust postnatal screening platform for somatosensory genomics and identifies Creld1 as a master regulator of somatosensory function, and provides novel therapeutic strategy for pain and itch treatment.

neuroscience↗

bioRxiv2026

A Novel Central-Peripheral Interface: The Auditory Nerve Glial Transition Zone Exhibits Enhanced Age-Related Immune and Glial Cell Dysfunction

Age-related hearing loss (ARHL) is a rapidly growing public health concern, affecting two-thirds of adults over 65 years old, with no effective therapeutics available. As the aging population grows at an unprecedented rate, the burden of ARHL will only increase. The causes of ARHL are multifactorial, but an understudied major contributor is glial dysfunction. The auditory nerve (AN) conducts sound from the cochlea to the brainstem and holds a diverse population of immune cells and myelinating glia. As the AN fibers bundle together within the cochlea to project to the brainstem, they are first myelinated by Schwann cells in the peripheral AN, then myelinated by oligodendrocytes in the central AN. The region where myelination shifts from Schwann cells to oligodendrocytes is the glial transition zone (GTZ), located in the cochlear modiolus, creating a unique biological niche. While central-peripheral interfaces are recognized in other cranial nerves, the AN GTZ is understudied. This region integrates the peripheral and central microenvironments within the confined bony cochlea, positioning it as a niche for glial dysfunction in pathological conditions, such as aging. We hypothesize that the GTZ is a site of enhanced glial dysfunction contributing to age-related AN demyelination, an important contributor to ARHL. We evaluated this in an ARHL mouse model combining RNA-sequencing, quantitative immunohistochemistry, and 3D high-resolution imaging. We examined the AN GTZ from human temporal bone donors. RNA-sequencing of the AN revealed age-associated increases in abnormal myelination/glial function and inflammation. There was a significant age-dependent increase in Iba1+ macrophages/microglia, with accumulation at the AN GTZ, and an increase in cellular volume and surface area, suggesting greater age-related activation. Macrophages/microglia contained significantly more internalized myelin debris in the AN (peripheral, central, and GTZ) with aging. More importantly, we found structurally intact myelin within macrophages/microglia only at the GTZ, suggesting a unique microenvironment at the GTZ altering phagocytic activity in aging. Together, our data suggest that the GTZ, a previously unrecognized central-peripheral interface, is a critical site of immune-glial interactions and especially vulnerable to age-related demyelination and neuroinflammation. This study highlights the GTZ as a potential target for preserving AN myelination and mitigating ARHL.

neuroscience↗

bioRxiv2026

Integration of large, complex single-cell datasets with Harmony2

Integrating single cell RNA-seq profiles is posing new challenges as datasets are rapidly expanding, now with over 100 million cells in the public domain. We present the latest version of the Harmony integration software, which efficiently scales to >100M cells and >1K datasets without specialized hardware. Moreover, optimizations to the underlying algorithm help prevent overintegration in biologically heterogeneous datasets. Harmony2 enables efficient, accurate integration of large, complex single-cell atlases.

bioinformatics↗

bioRxiv2026

Neutrophil-targeted delivery of circSCMH1 unlocks an acute anti-thromboinflammatory function to restore microvascular perfusion in stroke

ObjectivesFutile recanalization (FR) after endovascular thrombectomy (EVT) is driven by neutrophil-mediated thromboinflammation, yet conventional neuroprotectants fail to address the spatiotemporal complexity of stroke injury. This study aimed to identify the clinical link between circSCMH1, traditionally viewed as a late-stage repair molecule, and FR, while evaluating its hyperacute anti-inflammatory potential via a neutrophil-targeted delivery system. MethodsWe analyzed thrombi and plasma from LVO-AIS patients stratified by functional outcomes. We engineered neutrophil-targeted lipid nanoparticles (circSCMH1@pepLNP) for delivery in a mouse transient middle cerebral artery occlusion model. Therapeutic outcomes were evaluated through infarct volume measurement, histological assessment of NETosis, and intravital two-photon microscopy to monitor real-time neutrophil dynamics and capillary stalling. ResultsClinical analyses showed circSCMH1 was significantly downregulated in FR patients, with its levels negatively correlated with NET burden. Furthermore, circSCMH1-negative neutrophils exhibited a higher propensity for NETosis within the thrombus microenvironment. In mice, circSCMH1@pepLNP achieved specific neutrophil delivery, significantly reduced infarct volume, and suppressed the expression of citrullinated histone H3 and neutrophil elastase. Intravital two-photon and laser speckle imaging further confirmed that this intervention attenuated neutrophil adhesion, increased migratory velocity, and alleviated capillary stalling, thereby restoring cortical microvascular perfusion. ConclusionsOur findings associate neutrophil-specific circSCMH1 downregulation with clinical FR in LVO-AIS. Targeted intracellular delivery reveals an acute anti-thromboinflammatory function that complements established reparative properties, proposing a novel adjunctive approach for EVT to address the spatiotemporal complexity of stroke and improve clinical outcomes.

neuroscience↗

bioRxiv2026

Caveolin-1 Mediated Blood-brain Barrier Transcytosis Promotes Porphyromonas gingivalis Invasion and Alzheimer's Disease-Like Changes

Pathogens such as Porphyromonas gingivalis (P. gingivalis) may lead to Alzheimers disease (AD), but how they get into the brain and cause AD remains unclear, especially their level in blood is usually low. AD involves early breakdown of the blood-brain barrier (BBB). BBB disruption may allow blood-derived neurotoxic components to penetrate the BBB and enter the brain. We investigated whether BBB disruption permits P. gingivalis to enter the brain and accelerate disease-related changes. Using animal models, human BBB organoids and bEnd.3 cells, we found that a leaky BBB, especially through increased caveolin-1-dependent transcytosis, allowed P. gingivalis to cross into the brain. The bacteria triggered the hyperphosphorylation of Tau protein, increased A{beta} levels, and sustained neuroinflammation via activated glial cells. These findings indicate that BBB dysfunction facilitates P. gingivalis invasion, creating a vicious cycle of infection and neurodegeneration that may drive AD progression.

neuroscience↗

bioRxiv2026

Exercise-conditioned tear fluid suppresses myopia progression

Myopia represents a major global public health challenge with rapidly rising prevalence. It is thus important to explore novel therapeutics for the treatment of myopia. Here we predicted tear fluid after (TA) but not before (TB) moderate-intensity aerobic exercise might protect against myopia using reverse transcriptomic analysis. To experimentally validate this hypothesis, TA or TB was administered by periocular injection in a guinea pig model of form-deprivation myopia. As a result, TA treatment significantly attenuated myopic refractive shifts and suppressed vitreous chamber depth and axial length elongation, whereas TB showed no protective effects. This study proposes a novel therapeutic avenue for myopia intervention and also suggests a previously unrecognized tear fluid-mediated mechanism linking exercise to myopia.

bioinformatics↗

bioRxiv2026

Targeting AKAP13 RhoGEF activity ameliorates pro-fibrotic phenotypes driven by the IPF associated AKAP13 risk variant

RationaleIdiopathic pulmonary fibrosis (IPF) is a progressive, incurable scarring disease of the lung. A common genetic variant near AKAP13, a multifunctional scaffold protein that integrates intracellular signalling through its interactions with RhoA and protein kinase A (PKA), has been associated with IPF susceptibility and elevated AKAP13 mRNA expression in lung tissue from patients. However, its contribution to the pathogenesis of IPF remains unclear. ObjectiveThis study investigates how an AKAP13 variant alters epithelial signalling and evaluates the therapeutic potential of targeting AKAP13. Findingsrs62025270-bearing iHBECs exhibited selective upregulation of AKAP13 isoforms, accompanied by increased cell adhesion and reduced proliferation. Transcriptomic profiling revealed upregulated fibrosis-related genes in rs62025270-bearing iHBECs, including SAA1, FGF2, MMP1, CTSB, COL4A1, and CDKN1A. rs62025270-bearing iHBECs also displayed increased RhoA activation and SMAD2 phosphorylation following LPA stimulation. Furthermore, cells harbouring the AKAP13 variant showed reduced intracellular cAMP levels. Pharmacological inhibition of AKAP13 with A13 reversed the pro-adhesive phenotype and reduced RhoA activation in iHBECs. Moreover, in IPF-derived PCLS, A13 suppressed SERPINE1, CCN2, and MMP7 expression, reduced SMAD2 nuclear translocation, and decreased hydroxyproline levels. ConclusionsPresence of an AKAP13 variant disrupts epithelial homeostasis and promotes pro-fibrotic signalling. Inhibition of AKAP13s RhoGEF domain with A13 restores epithelial function and attenuates fibrotic activation, supporting AKAP13 as a therapeutic target in IPF.

genetics↗

bioRxiv2025

Preclinical immunogenicity of the LP.8.1-adapted BNT162b2 COVID-19 vaccine

SARS-CoV-2 evolution toward antigenically distinct lineages drives escape from host immunity. JN.1 lineage derivatives have recently dominated the global epidemiologic landscape. In preclinical models, an LP.8.1-adapted BNT162b2 vaccine elicited higher serum neutralizing antibody responses against contemporary, circulating JN.1 sublineages, including the currently dominant XFG, as compared to JN.1-, KP.2- and XEC-adapted vaccines. These findings supported the selection of an LP.8.1-adapted vaccine for the composition of the 2025-26 COVID-19 vaccine formula.

immunology↗

bioRxiv2025

R-loops orchestrate the maternal-to-zygotic transition by harnessing RNA polymerase II pause release

R-loops, ubiquitous three-stranded nucleic acid structures abundant in the mammalian genome, play pivotal roles in diverse biological processes1-3. However, the dynamics and functions of R-loops during mammalian preimplantation embryonic development remain poorly understood. Here we optimized an innovative, ultra-sensitive RIAN-seq method capable of mapping genome-wide R-loop landscape using ultra-low cell numbers to investigate R-loop dynamics in mouse gametes and early embryos. Our findings reveal the widespread presence of AT-rich R-loops during early mouse embryonic development and highlight their critical roles in orchestrating transcription machinery during zygotic genome activation (ZGA). We demonstrate that the stability and inheritance of R-loops through developmental stages are governed by their sequence composition, with GC-rich R-loops exhibiting greater stability. Notably, R-loops, particularly AT-rich R-loops, inhibit DDX21 helicase activity on the 7SK/HEXIM1 snRNP complex, thereby reducing CDK9 release. This, in turn, modulates the phosphorylation of Ser2 at C-terminal domain (CTD) of RNA polymerase II (RNAPIIS2p) at the promoters of major ZGA and maternal genes. Furthermore, R-loops promote RNAPII accumulation at major ZGA gene promoters, preventing RNAPII from premature release and ensuring timely activation of major ZGA genes. Conversely, R-loops enhance the retention of stalled RNAPII at maternal gene promoters, effectively repressing their expression and facilitating the maternal-to-zygotic transition. In summary, our study unveils a key role for R-loops in regulating the maternal-to-zygotic transcription transition and early embryonic development in mice.

developmental biology↗

bioRxiv2025

PHOX2B polyalanine repeat mutation has a profound impact on the transcriptome of neuronal progenitor cells in Haddad syndrome

Mutation in paired-like homeobox 2B (PHOX2B) is used as the diagnostic marker of Haddad syndrome (HS). The mutant gene/protein afflict neural crest cells during embryonic development which leads to congenital central hypoventilation syndrome (CCHS) and Hirschsprungs disease (HSCR). Previous studies on HS and CCHS have mainly focused on the conformational dynamics of the mutant protein and have remained controversial. Here we performed RNA-sequencing on the patient derived neuroepithelial stem cells (NESCs), pertinent to the neurodevelopmental phenotype in HS, and found that the PHOX2B-PARM has a profound impact on the transcriptional profile of the cells. The single copy of PHOX2B-PARM in heterozygote cells were leading to >10 fold differentially expressed genes. In the patient cells there was a significant enrichment of genes related to neuronal development and synapse organization mainly driven by L1CAM interactions and synaptogenesis signaling pathway. Our result not only highlight the use of a suitable model of HS but also provide a clear path for future experimental validation and downstream targets with potential therapeutic values.

neuroscience↗

bioRxiv2025

N6-Methyladenine DNA modification regulates pathogen virulence in nematodes

Understanding the global regulatory mechanisms that control pathogen virulence gene expression is essential for elucidating the molecular basis of pathogenicity. N6-methyladenine (6mA) plays a crucial role in regulating gene expression in response to various environmental stresses; however, its role in pathogen virulence remains largely unexplored. Here, we report the widespread occurrence of 6mA across 17 nematode isolates and map its genomic landscape in six notorious agriculturally important pathogen root-knot nematodes (RKNs). We demonstrated that 6mA is characterized by a conserved GAG motif across nematodes, but exhibits species-specific distribution patterns and distinct effects on gene expression. In particular, its enrichment in transposable elements differs between polyploid and diploid nematodes, suggesting lineage-specific epigenetic regulation potentially associated with polyploidy. We further identified two functional 6mA demethylases, MiNMAD-1 and MiNMAD-2, and confirmed their catalytic activity and active sites. Host-induced gene silencing of minmad-1 significantly increased plant resistance to three polyploid RKN species. A detailed functional analysis revealed that minmad-1 knockdown disrupted virulence gene expression during the parasitic stage, thereby reducing nematode infectivity. Together, our findings suggest 6mA demethylase as a key epigenetic regulator of RKNs virulence, providing new insights into nematode biology and offering promising targets for the development of sustainable control strategies. Significance Statement6mA methyltransferase regulates the expression of virulence genes in certain pathogenic bacteria and plays a critical role in their infectivity. However, the regulation of virulence gene expression in eukaryotic pathogens, particularly plant pathogens, remains poorly understood. Most studies on pathogen virulence have focused on individual effectors, with little insight into global regulatory mechanisms. Here, we demonstrate that 6mA broadly shapes virulence gene expression patterns in polyploid RKNs. Moreover, transgenic tobacco, tomato, and rice plants expressing dsRNA against nematode demethylases showed significantly enhanced resistance to RKNs. These findings establish 6mA demethylase as a promising epigenetic target for controlling plant-parasitic nematodes.

molecular biology↗

bioRxiv2025

Distinct contributions and sensorimotor encoding of PV and FoxP2 neurons in the external globus pallidus during perceptual decision-making

The external globus pallidus (GPe), a central nucleus of the basal ganglia (BG), comprises diverse cell types, including PV and FoxP2 neurons. While their roles in movement regulation and sensory processing have been studied, their contributions to perceptual decision-making remain unclear. Using a Go/No-Go visual task in mice, we found that optogenetic activation of either population impaired behavioral performance, whereas only inhibition of PV neurons, but not FoxP2 neurons, disrupted behavior. Electrophysiological recordings revealed that PV and FoxP2 neurons exhibited distinct encoding of visual stimuli, licking movement, and trial outcomes, with a larger fraction of PV neurons positively encoding the reward-predicting (Go) stimulus and the population overall preferring the rewarded over unrewarded outcome. FoxP2 neuron inhibition had minimal effects on spontaneous firing of neurons in the substantia nigra pars reticulata (SNr), a major BG output. By contrast, PV neuron inhibition altered both spontaneous and task-related activity of SNr neurons, reducing their preference for reward-predicting stimulus or unrewarded outcome in a subpopulation-specific manner. These findings indicate that PV and FoxP2 neurons in the GPe differentially influence sensorimotor processing and SNr activity, with PV neurons playing a key role in supporting accurate performance during perceptual decision-making.

neuroscience↗

bioRxiv2025

Multiscale 3D whole joint cellular and molecular mapping dissects the relationship between structure and pain

Understanding musculoskeletal joints from a 3D multiscale perspective, from molecular to anatomical levels, is essential for resolving the confounding relationships between structure and pain, elucidating the intricate mechanisms regulating joint health and diseases, and developing new treatment strategies. Here, we introduce a musculoskeletal joint immunostaining and clearing (MUSIC) method specifically designed to overcome key challenges of immunostaining and optical clearing of intact joints. Coupled with large-field light sheet microscopy, our approach enables 3D high-resolution, microscale neurovascular mapping within the context of whole-joint anatomy without the need for image coregistration across various joints, including temporomandibular joints, knees, and spines, and multiple species, including mouse, rat, and pig. Our findings reveal 3D heterogeneous distributions of neurovascular networks and previously uncharacterized neurovascular pathways within joints. Using the proteoglycan 4 knockout (Prg4-/-) mouse model of joint degeneration, we identified significant alterations in joint-wide neurovascular architecture, highlighting neurovascular changes along degenerative processes. Furthermore, in a traumatic joint injury mouse model, we observed long-lasting pain behavior and a time-course 3D neurovascular remodeling preceding detectable joint morphological change, bridging microscale alterations with potential pain mechanisms. This platform offers a powerful tool for multiscale 3D analysis, enabling new insights into joint pathophysiology and intricate interplay among joint tissues.

bioengineering↗

bioRxiv2025

Functional loss of CHS2 confers high levels resistance to Bacillus thuringiensis Vip3Aa, but with significant fitness costs in five lepidopteran species

Bacillus thuringiensis (Bt) crops, engineered to produce insecticidal proteins such as Vip3Aa and Cry toxins, have revolutionized pest management by providing a sustainable alternative to chemical pesticides. However, the development of resistance to these toxins has driven the investigation of underlying mechanisms to better understand how pests evade toxicity and to develop more effective resistance management strategies. Recently, a laboratory-selected Spodoptera frugiperda strain exhibited a high level of resistance to Vip3Aa (resistance ratio: 5562-fold), with the mutation of the chitin synthase gene, SfCHS2, identified as a key factor. In this study, we extend these findings to additional lepidopteran species, including Spodoptera exigua and Agrotis ipsilon. Our results show that CHS2 knockout strains lack the peritrophic matrix (PM), while the resistant Sfru_R3 strain retains its PM. Knockout of this gene resulted in high levels resistance to Vip3Aa. These findings further validate the role of the CHS2 gene in Vip3Aa resistance and highlight its potential as a target for resistance management in lepidopteran pests. This study advances our understanding of the molecular mechanisms behind resistance to Vip3Aa and supports the development of strategies to delay resistance in Bt crop management.

genetics↗

bioRxiv2025

Unveiling the Developmental Dynamics and Functional Role of Odorant Receptor Co-receptor (Orco) in Aedes albopictus: A Novel Mechanism for Regulating Tuning Odorant Receptor Expression

As one of the most aggressive disease vectors, the Asian tiger mosquito Aedes albopictus relies heavily on its olfactory system to search for food in the larval stage, locate hosts after eclosion, and identify suitable oviposition sites after blood feeding. In mosquitoes and other insects, the olfactory system detects environmental odors primarily through a diverse repertoire of tuning odorant receptors (ORs), which require the highly conserved odorant receptor co-receptor (Orco) to function. While Orcos role in enabling tuning receptor function is well established, its cellular localization patterns, developmental expression dynamics, and system-wide impact on olfactory physiology and behavior remain understudied in Ae. albopictus. To address this knowledge gap, we leveraged the Q-system to systematically characterize Orco-expressing neurons (ORNs) across embryonic, larval, pupal and adult stages of Ae. albopictus. We uncovered a dramatic reorganization of the olfactory system during metamorphosis: ORNs were observed as early as the embryonic stage and expanded during larval development before rapid degeneration and re-generation in the pupal stage resulting in the final population of adult ORNs. Orco expression in adults spanned the olfactory neurons of the antennae, labella, and maxillary palps in both male and female mosquitoes, consistent with its conserved peripheral distribution. To further investigate the functional implications of Orco, we generated Orco knockout mutants and strikingly discovered that Orco knockout mutants displayed significant widespread downregulation of tuning Ors, suggesting that Orco may influence OR expression or stability. Electrophysiological recordings confirmed significantly attenuated responses to human volatiles in Orco mutants, and behavioral assays demonstrated a marked decline in blood-feeding efficiency and elimination of host preference in females. Together, these findings reveal dynamic reorganization of ORNs during mosquito development and uncover the critical role of Orco in maintaining the integrity and function of the olfactory system, providing insights that may inform novel, next-generation vector control strategies.

neuroscience↗

bioRxiv2025

Characterization of hyperoxia-induced senescent lung macrophages in neonatal mice

Bronchopulmonary dysplasia (BPD), a chronic lung disease in premature infants, results from mechanical ventilation and hyperoxia amongst other factors. We and others have shown that neonatal hyperoxia, known to lead to a BPD-like phenotype in rodent models, causes lung cellular senescence. In our 3-day hyperoxia model, the majority of senescent cells were lung macrophages, and these peaked at postnatal day (pnd) 7. The features of these senescent macrophages are not characterized. Here, we reanalyzed scRNA-seq datasets (GSE207866) of senescent lung cells from mice exposed to hyperoxia as neonates at pnd7 (SD7), and characterized their gene express profiling and compared them with air control (AirD7) and hyperoxia-exposed group without isolation of senescent cells at pnd7 (O2D7). We first classified the cells into epithelial, endothelial, immune, and mesenchymal cells to extract immune cells. By employing the workflow to the immune clusters, mixed populations of macrophages, monocytes, and dendritic cells and pure population of macrophages, we finally identified seven clusters of macrophages. In SD7 group, 65.9% senescent cells were macrophages, and comprised M1 (64%) and alveolar (62.8%) macrophages. Clusters 0 and 1 were M1 and alveolar macrophages, which were composed of 49.2% of senescent macrophages. These two clusters highly expressed genes involved in innate immunity, inflammation, DNA repair response and phagocytosis. Metabolic switch from mitochondrial respiration to glycolysis and pentose phosphate pathway was observed in these two clusters. Conclusively, senescent macrophages are heterogenous with distinct tissue compartments and metabolic dysregulation.

cell biology↗

bioRxiv2025

Respiratory Airway Secretory Cells act as Immune Sentinels in Human Distal Airways

Pulmonary immunity in the human distal respiratory airways is essential for lung function but remains poorly explored, mainly due to limited physiologically relevant models. Here, we develop distal lung organoids containing respiratory airway secretory (RAS) cells, a recently identified epithelial population unique to the distal airways of humans and large mammals, using human pluripotent stem cells (hPSCs). Lineage tracing identified RAS cells as descendants of SOX9brightNKX2-1bright progenitors. Single-cell transcriptomics elucidated that RAS cells exhibited a distinct immune-competent phenotype with enriched genes associated with viral host entry and pattern recognition receptor signaling. Functionally, RAS cells infected by respiratory syncytial virus (RSV) exhibited enhanced antiviral activity marked by upregulation of interferon-stimulated genes (ISGs) and complement component 3 (C3). In contrast, bacterial flagellin or Pseudomonas aeruginosa (PAO1) triggered a TLR5-driven immune response in RAS cells, inducing complement system activation, a response suppressed by selective TLR5 inhibition. Notably, in chronic obstructive pulmonary disease (COPD), RAS cells displayed dysregulated immune activation, characterized by elevated expression of adaptive immune mediators. Together, our findings identify RAS cells as previously unrecognized sensors and effectors of mucosal immunity in the human distal airways and reveal their roles in viral infection, bacterial stimulation, and chronic inflammatory lung disease, providing potential therapeutic targets for respiratory diseases.

cell biology↗

bioRxiv2025

High-Quality Cell Capture Reveals Transcriptomic Changes After Single-Axon Injury of Mauthner Cells

In vivo single-cell capture methods based on micropipettes are essential for correlating morphological characteristics with transcriptomic profiling under physiological conditions. However, they often suffer from significant contamination of off-target cells. Consequently, we developed Hip-seq, which significantly reduces heavily contaminated cells, decreases contamination levels, improves cell reproducibility, and enhances data analysis accuracy compared to patch-seq. Using Hip-seq, we found that axon regeneration failure could be due to abnormal activation of translation and the circadian clock. Axon-regenerable central neurons reactivated axon development-related genes during regeneration. And one-to-one associated analysis helped identify pro-regenerative genes.

neuroscience↗