Biology subjects

Lin, Q.

Publications and source records attributed to Lin, Q..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Identification of QTLs for Internode Length and Diameter Associated with Lodging Resistance in Rice

Lodging is a significant challenge in rice production, particularly for high-yielding cultivars. Previous research has shown that stem characteristics, such as internode length and diameter, are key determinants of lodging resistance. However, the genetic mechanisms controlling these traits remain poorly understood. To investigate the genetic basis of lodging-related stem traits, a recombinant inbred line (RIL) population was developed from a cross between Zhenshan 97 and C309, two rice varieties with contrasting stem architectures. A high-density genetic linkage map was constructed using 3,307 bin markers generated by next-generation sequencing. Comprehensive phenotypic analysis was conducted for heading date, internode length, and diameter. A total of 54 quantitative trait loci (QTLs) were identified across the genome. Importantly, 15 pleiotropic QTLs were detected, each affecting multiple internode-related traits. These pleiotropic loci include well-known functional genes such as SCM2 and Gn1a, as well as several novel loci potentially involved in regulating stem strength and lodging resistance. Additionally, RNA-Seq analysis was performed to identify candidate genes associated with these traits. Among the 1,263 expressed genes within the 15 pleiotropic QTL regions, 183 differentially expressed genes were identified. LOC_Os06g11130 was highlighted as a key gene for further investigation. Haplotype analysis and linkage disequilibrium analysis revealed significant haplotype variation in LOC_Os06g11130, further confirming its potential role in lodging resistance. This study enhances our understanding of the genetic architecture of internode traits associated with lodging resistance in rice. The identification of pleiotropic and major-effect QTLs provides valuable genetic resources for marker-assisted selection and genomic breeding, with the potential to improve lodging resistance in high-yielding rice cultivars. These findings contribute to the development of rice varieties that balance high yield potential with enhanced lodging resistance.

genetics↗

bioRxiv2025

Identification and characterization of emNagⅡ, a novel β-1,2-N-acetylglucosaminidase from Elizabethkingia meningoseptica

N-Acetylglucosamine exists in various forms and linkage patterns within organisms, playing a crucial role in numerous vital biological processes. However, research focusing on {beta}-1,2-linked N-acetylglucosamine within complex biantennary N-glycans on the cell surface remain largely unexplored. Currently, there is a lack of efficient tools and methods capable of directly modifying terminal N-acetylglucosamine on living cells. In this study, we identified a novel {beta}-N-acetylhexosaminidase from Elizabethkingia meningoseptica, which demonstrated favorable enzymatic stability within a pH range of 5-8 and at temperatures from 4 {degrees}C to 37 {degrees}C. This enzyme specifically cleaves non-reducing terminal {beta}-1,2-N-acetylglucosamine, enabling direct removal of this modification from oligosaccharides and native glycoproteins. More importantly, we demonstrate for the first time that this enzyme successfully removes {beta}-1,2-linked N-acetylglucosamine on living cell surfaces. Given its microbial origin and potential utility in living cell glycan editing, we have named it emNagII or cell-surface glycan-editing N-acetylglucosaminidase (csgeNagII). Through sequence analysis and alanine scanning mutagenesis, we identified a predicted active pocket containing the catalytic residue pair Asp317-Glu318, with Asp317 being essential for enzymatic activity. In summary, our findings provide an effective and reliable method for the targeted removal of {beta}-1,2-N-acetylglucosamine on living cell surfaces, establishing a foundation for further functional studies and practical applications.

biophysics↗

bioRxiv2025

Placing very long branch taxa in the plant tree of life: a case study with Dioscoreales mycoheterotrophs

PremiseThe inclusion of heterotrophic plants in broadly focused systematic studies is challenging, reflecting substantial morphological modification, gene loss, and accelerated nucleotide substitution following photosynthesis loss. In particular, inclusion of very long branch (VLB) taxa with highly elevated rates may lead to phylogenomic misinference. MethodsWe explore how rapidly evolving plastomes behave in model-based phylogenetic inferences of the yam order Dioscoreales, which experienced convergent photosynthesis losses. The taxon sampling includes all photosynthetic genera, and mycoheterotrophic lineages with a broad range of substitution rates. ResultsWhen only moderately rapidly evolving heterotrophs are included, relationships within Dioscoreales are congruent with recent mitochondrial analysis, and generally strongly supported. Photosynthetic Stenomeris (represented by only three genes) is moderately supported as sister to Dioscoreaceae. Notably, Burmanniaceae and Thismiaceae, two mycoheterotrophic families including highly reduced plastomes, are strongly supported as distantly related within Dioscoreales. Constrained analysis rejects combining Thismiaceae with Burmanniaceae, conflicting with current angiosperm classification. Including VLB mycoheterotrophs in phylogenetic inference can lead to localized to broad reduction in branch support--substantially so for Afrothismiaceae, a family placing in disparate locations in Dioscoreales (and beyond) in variant analyses, with no ability to differentiate among its alternative placements. ConclusionsInclusion of highly rate-elevated taxa in analyses of Dioscoreales phylogeny can depress branch support. Inferred relationships in the order are otherwise congruent with studies based on mitochondrial data; the family-level classification needs updating. The extraordinarily rapidly evolving family Afrothismiaceae places inconsistently in diverse plastid analyses, pointing to probable analytical limits for plastid-based phylogenomic analyses of VLB heterotrophs.

evolutionary biology↗

bioRxiv2025

Therapeutic Salmonella induces long-term protective trained immunity in NK cells against cancer metastasis

Trained immunity, a form of innate immune memory initially recognized in pathogen defense, has recently been reported to aid in combating cancer. Although trained immunity has been well-characterized in myeloid lineage cells, its presence in innate lymphoid cells, particularly natural killer (NK) cells, remains largely unexplored. Here, we report that a single dose of Salmonella YB1, an attenuated candidate anticancer vaccine strain, provides long-lasting protection against cancer metastasis in mice by inducing trained natural killer (NK) cells. Functional assays coupled with multiomics analysis revealed that Salmonella-trained NK (stNK) cells establish an enduring reprogrammed epigenome characterized by enhanced pro-survival signaling and immune effector functions, resulting in more potent IFN-{gamma} release and cytotoxicity upon secondary stimulation. We further revealed that IL-12 and IL-18 are essential but insufficient for this NK cell training effect. Crucially, stNK cells far outperform the common immune checkpoint therapies, including PD-1 and TIGIT blockade, in suppressing metastasis, underscoring the unique immunological mechanisms in combating metastasis. These findings uncover a novel long-term anti-metastatic function of trained immunity in NK cells, highlighting its potential as an effective antitumor strategy.

immunology↗

bioRxiv2025

Identification and characterization of a novel exo-glycosidase activity of NGLY1 on ENGase-digested N-GlcNAc proteins in vitro

N-Glycanase 1 (NGLY1) is known for its activity to completely remove conjugated N-glycans from glycoproteins. Early studies illustrated that NGLY1 defects were associated with a rare disease named NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG). Although extensive research has been conducted over the past decade on the biological impact of NGLY1s endo-(N-)glycanase activity in cells and on disease, whether NGLY1 also exhibits an exo-(N-)glycanase activity remains open. In this study, an exo-(N-)glycanase activity of NGLY1 on the N-GlcNAc proteins was firstly reported and characterized in vitro. To distinguish for the conventional endo-(N-)glycanase activity and the newly reported exo-(N-)glycanase activity of NGLY1, the active sites of exo-NGLY1 were predicted and compared with those of endo-NGLY1. In addition, the correlation between NGLY1s exo-(N-)glycanase activity in vitro and NGLY1-CDDGs clinical characterization was investigated and discussed. The observation of NGLY1s novel exo-(N-)glycanase activity expanded the functional repertoire of NGLY1 beyond canonical endo-(N-)glycanase-mediated deglycosylation, and may provide a new framework to explain the clinical heterogeneity of NGLY1-CDDG.

biochemistry↗

bioRxiv2025

An atlas of cell type specific regulatory effects in cattle

Understanding the genetic and molecular architecture of complex traits and artificial selection is crucial for advancing sustainable precision breeding in cattle and other livestock. Yet, how genetic variation affects cellular gene expression remains elusive in cattle. Here, by integrating 8,866 bulk RNA-seq samples and 999,192 single cells of 81 cell types in 22 bovine tissues, we presented a comprehensive atlas of regulatory variants at the cell type resolution in cattle. By colocalizing with bulk-tissue expression quantitative trait loci (beQTL), we detected 57,043 novel cell-type stratified eQTL and cell-type/state interaction eQTL in 18,153 genes, which also exhibited a stronger tissue/cell-type specificity than beQTL. By examining genome-wide associations (GWAS) of 44 complex traits, these cell-resolved eQTL were colocalized with 505 (24%) additional GWAS loci compared to beQTL. Through integrating this resource with selection signatures between dairy and beef cattle, we provided tissue/cell-specific regulatory insights into cattle breeding. Overall, the current atlas of cell-type-specific regulatory variants will serve as an invaluable resource for cattle genomics and selective breeding.

genetics↗

bioRxiv2025

Synthesizing human-specific spike-in standards for RNA-seq experiments and assessing their technical performance

Using spike-in standards for RNA-seq experiments is critical to evaluate technical bias introduced during sample preparation, sequencing and analysis. Although some external RNA spike-in standards have been developed, species-specific spike-in standard was not reported yet. Here we developed the human-specific spike-in standards with 65 controls. We first extracted human endogenous RNAs with various lengths and GC contents, introduced random mutations approximately every 75 bp in each RNA, and then synthesized these RNAs as spike-in RNAs. After that, four mixtures of these spike-in RNAs covering a 220 dynamic range were obtained. To ensure the accuracy of RNA concentration, two rounds of ddPCR were conducted for each spike-in RNA and the intraclass correlation coefficient between two ddPCRs ranged from 0.9954 to 0.9971 after removing the two spike-in RNAs with the largest concentration difference. Furthermore, we showed that the sequencing error profiles were distinct between platforms and the library preparation procedures were related with the discrepancies in spike-in RNA read percent, transcript abundance, sequence coverage distribution, and differential gene expression. In addition, two regression models of sequence coverage were built based on RNA second structure and GC content, and 86.62%-91.78% of the variation can be explained. Our study demonstrates the technical performance of the human-specific spike-in standards for RNA-seq experiments and illustrates the biases across different libraries, platforms, and laboratories.

bioinformatics↗

bioRxiv2025

Calcium channel-coupled transcription factors facilitate direct nuclear signaling

VGCCs play crucial roles within the CNS, in maintaining cell excitability, enabling activity- dependent neuronal development, and forming long-term memory by regulating Ca2+ influx. The intracellular carboxyl-terminal domains of VGCC 1 subunits help regulate VGCC function. Emerging evidence suggests that some VGCC C-termini have functions independent of channel gating and exist as stable proteins. Here, we demonstrate that all VGCC gene family members express bicistronic mRNA transcripts that produce functionally distinct C-terminal proteins (CTPs) in tandem with full-length VGCC 1 subunits. Two of these CTPs, 1CCT and 1ACT, cycle to and from the nucleus in a Ca2+- and calmodulin-dependent fashion. 1CCT, 1ACT, and 1HCT regulate chromatin accessibility and/or bind directly to genes, regulating gene networks involved in neuronal differentiation and synaptic function in a Ca2+-dependent manner. This study elucidates a conserved process of coordinated protein expression within the VGCC family, coupling the channel function with VGCC C-terminal transcription factors.

neuroscience↗

bioRxiv2024

Shroom3-Rock interaction and profibrotic function: Resolving mechanism of an intronic CKD risk allele.

Common intronic enhancer SNPs in Shroom3 associate with CKD in GWAS, although there is paucity of detailed mechanism. Previously, we reported a role for Shroom3 in mediating crosstalk between TGF{beta}1- & Wnt/Ctnnb1 pathways promoting renal fibrosis (TIF). However, beneficial roles for Shroom3 in proteinuria have also been reported suggesting pleiotropic effects. Here we focused on identifying the specific profibrotic Shroom3 motif. Given known therapeutic roles for Rho-kinase inhibitors in experimental CKD, and the established interaction between Shroom3 and Rock via its ASD2 domain, we hypothesized that Shroom3-mediated ROCK activation played a crucial role in its profibrotic function in high expressors. To test this hypothesis, we developed transgenic mice and cell lines that inducibly overexpressed wild-type- (WT-Sh3) or ASD2-domain deletion- Shroom3 (ASD2{Delta}-Sh3). Prior scRNAseq data showed that during TIF, Shroom3 and Rock co-expression occurred in injured tubular cells and fibroblasts, highlighting cell-types where this mechanism could be involved. Using HEK293T cells, we first confirmed absent ROCK binding and inhibited TGF{beta}1-signaling with ASD2{Delta}-Sh3-overexpression vs WT-Sh3. In mIMCD cells, ASD2{Delta}-Sh3 overexpression, reduced Rock activation (phospho-MYPT1), pro-fibrotic and pro-inflammatory transcripts vs WT-Sh3. Fibroblast proliferation (3T3) was also reduced with ASD2{Delta}-Sh3. In vivo, we studied ureteric obstruction (UUO) and Aristolochic nephropathy (AAN) as TIF models. In AAN, inducible global-, or Pan-tubular specific-, WTSh3-overexpression showed increased azotemia, and TIF vs ASD2{Delta}-Sh3 mice. WT-Sh3 mice consistently showed significant enrichment of Rho-GTPase, TGF{beta}1- and Wnt/CtnnB1- signaling in kidney transcriptome, paralleling Shroom3-coexpressed genes in tubulo-interstitial transcriptomes from human CKD. In UUO, again WT-Sh3 mice recapitulated increased fibrosis vs ASD2{Delta}-Sh3. Importantly, ASD2{Delta}-Sh3 did not develop albuminuria vs WT-Sh3, while mutating a disparate Fyn-binding Shroom3 motif induced albuminuria in mice, suggesting motif-specific roles for Shroom3 in the kidney. Hence, our data show a critical role for the Rock-binding, ASD2-domain in mediating TIF in milieu of Shroom3 excess, with relevance to human CKD.

systems biology↗

bioRxiv2024

Delineation of Single-cell Altas Provides New Insights for Development of Coronary Artery Lesions in Kawasaki Disease: Bad and Good Signaling Molecules

BackgroundKawasaki Disease (KD) is a vasculitis syndrome featured with a high and persistent fever and mainly affects children under 5 years of age. It is the leading cause of acquired heart disease in the form of coronary artery lesions (CALs) for children in developed countries. Most KD can be relieved with the high-dosage Intravenous immunoglobulin (IVIG) therapy, but a small proportion develop CALs after IVIG treatment. MethodsWe performed the single-cell RNA sequencing for the peripheral blood mononuclear cells (PBMCs) from three KD non-CAL patients whose samples were acquired before and after IVIG treatment and three KD CAL patients whose samples were acquired only after IVIG treatment. Cell-to-cell communication patterns were also analyzed in KD CAL and non-CAL patients ResultsOverall cell expression feature analyses show immunoglobulin and adaptive immunity related genes are upregulated in KD CAL patients while B cell activation related genes are downregulated in them. Pseudo-time analyses demonstrate that both KD non-CAL patients before treatment and KD CAL patients after treatment have a dysregulated B cell developmental trajectory while the former has a mixed T and B lineage and the latter has a mixed monocyte and B lineage. The early elevated expression of SPI1 could partly explain the dysregulated B cell development in KD CAL patients. Cell communication analyses propose a disorder cell communication pattern in KD non-CAL patients before treatment and some persistent bad cell-to-cell signals in KD CAL patients after treatment. There are four signaling molecules, APP, CCL, and MCH-II, whose expression is significantly increased in the CD14 and CD16 monocytes of KD CAL patients, where the expression of RESISTIN is significantly increased in those KD non-CAL patients. ConclusionsOur results suggest that APP, CCL, and MCH-II might be the bad signals for indicating the possible development of CAL while RESISTIN is a good one for protecting from CAL.

immunology↗

bioRxiv2024

Nascent transcript O-MAP reveals the molecular architecture of a single-locus subnuclear compartment built by RBM20 and the TTN RNA

Eukaryotic nuclei adopt a highly compartmentalized architecture that influences nearly all genomic processes. Understanding how this architecture impacts gene expression has been hindered by a lack of tools for elucidating the molecular interactions at individual genomic loci. Here, we adapt oligonucleotide-mediated proximity-interactome mapping (O-MAP) to biochemically characterize discrete, micron-scale nuclear neighborhoods. By targeting O-MAP to introns within the TTN pre-mRNA, we systematically map the chromatin loci, RNAs, and proteins within a muscle-specific RNA factory organized around the TTN locus. This reveals an unanticipated compartmental architecture that organizes cis- and trans-interacting chromosomal domains, including a hub of transcriptionally silenced chromatin. The factory also recruits dozens of unique RNA-binding and chromatin-scaffolding factors, including QKI and SAFB, along with their target transcripts. Loss of the cardiac-specific splicing factor RBM20--a master regulator of TTN splicing that is mutated in dilated cardiomyopathy--remodels nearly every facet of this architecture. This establishes O-MAP as a pioneering method for probing single-locus, microcompartment-level interactions that are opaque to conventional tools. Our findings suggest new mechanisms by which coding genes can "moonlight" in nuclear-architectural roles.

genomics↗

bioRxiv2024

Harnessing Smartphone RGB Imagery and LiDAR Point Cloud for Enhanced Leaf Nitrogen and Shoot Biomass Assessment - Chinese Spinach as a Case Study

Accurate estimation of leaf nitrogen concentration and shoot dry-weight biomass in leafy vegetables is crucial for crop yield management, stress assessment, and nutrient optimization in precision agriculture. However, obtaining this information often requires access to reliable plant physiological and biophysical data, which typically involves sophisticated equipment, such as high-resolution in-situ sensors and cameras. In contrast, smartphone-based sensing provides a cost-effective, manual alternative for gathering accurate plant data. In this study, we propose an innovative approach for estimating leaf nitrogen concentration and shoot biomass by integrating smartphone RGB imagery with Light Detection and Ranging (LiDAR) data, using Amaranthus dubius (Chinese spinach) as a case study. The influence of varying nitrogen dosages on individual spectral and structural features derived from smartphone RGB imagery and LiDAR data was modeled. Additionally, the spectral indices from RGB imagery and structural indices from LiDAR data were combined to model both leaf nitrogen concentration and shoot biomass. The performance of crop parameter modeling was evaluated using support vector regression, random forest regression, and lasso regression. Results demonstrate that the combined use of smartphone RGB imagery and LiDAR data can accurately estimate leaf total reduced nitrogen concentration, leaf nitrate concentration, and shoot dry-weight biomass, with average relative root mean square errors as low as 0.06, 0.16, and 0.05, respectively. Furthermore, the optimal nitrogen dosage for maximizing biomass yield in Chinese spinach was also estimated using the smartphone data. This study lays the groundwork for smartphone-based estimate leaf nitrogen concentration and shoot biomass, supporting accessible precision agriculture practices.

bioinformatics↗

bioRxiv2024

Nitrogen ionome dynamics on leafy vegetables in tropical climate

Nitrogen is known to be a critical macro-nutrient influencing plant physiology, growth, and mineral composition. In tropical conditions, which are challenging for leafy vegetable farming, the nitrogen delivery effect is unclear. In this study, we aimed to investigate the effect of nitrogen application on key physiological traits and the mineral composition of the plants, the plant ionome. Experiments were conducted under tropical conditions greenhouse with varying levels of nitrogen supply to examine the effect on plant transpiration, yield, use efficiency of water and nitrogen, and nutrient uptake dynamics followed by cross-correlation analysis, trying to understand the physiological behavior-uptake dynamics relationships. The results demonstrated that transpiration, yield and WUE theoretic optimum curve, which peaking in nitrogen concentration of 120 mg/L for Chinese spinach and 200 mg/L for Chinese broccoli. Conversely, NUE reduce significantly with increasing nitrogen delivery which reflected on antagonistic increase of excess nitrogen. In terms of mineral composition, nitrogen application resulted in an increase I nitrogen content in the plant leaf tissue, while concentration of certain macronutrients and micronutrients were affected, including potassium, phosphorus, calcium, magnesium, iron, zinc, and molybdenum. Part of the minerals exhibited decreasing pattern due to potential competitive uptake mechanism, iron revealed increasing pattern that correlated with nitrogen delivery, and some minerals correlated with the measured physiological parameters. These results underscore the importance of optimizing nitrogen fertilization to balance plant growth, physiological processes, and plant nutrient homeostasis. The study offers valuable insights for sustainable nitrogen management in agricultural systems aimed at maximizing crop yield while maintaining nutritional quality.

plant biology↗

bioRxiv2024

Deep Learning Driven Cell-Type-Specific Embedding for Inference of Single-Cell Co-expression Networks

The inference of gene co-expression module in specific cell types is important for understanding of cell-type-specific biological processes. We have developed DeepCSCN, an unsupervised deep-learning framework, to infer gene co-expression modules from single-cell RNA sequencing (scRNA-seq) data. Utilizing a global-to-local network construction approach, DeepCSCN can infer co-expression at the whole sample level and construct cell-type-specific co-expression networks. Systematic evaluations on eight public scRNA-seq datasets show that DeepCSCN significantly outperforms eight existing methods in co-expression network construction. Furthermore, DeepCSCN effectively identifies cell-type-specific co-expression networks that are more enriched for cell-specific functional pathways compared to current methods. Finally, application of DeepCSCN on public scRNA-seq data revealed 280 cell-specific gene modules across 27 cell types, including epithelial cells, immune cells, and myonuclei, demonstrating its versatility and accuracy in elucidating cell-type-specific gene co-expression regulation. DeepCSCN offers a powerful tool for researchers to dissect the intricate gene co-expression networks within distinct cell types.

bioinformatics↗

bioRxiv2024

BMAP: a comprehensive and reproducible biomedical data analysis platform

In the realm of biomedical research, efficient data analysis and processing are crucial due to the escalating volume and complexity of data generated by research teams. Managing these vast arrays of localized data presents significant challenges, necessitating precise, efficient, and reproducible analysis methodologies to ensure the integrity and reliability of scientific outcomes. Traditional management of analysis codes, computing environments, and the inherent difficulties in result traceability due to team dynamics often lead to inefficiencies and potential risks in maintaining academic integrity. Furthermore, while online storage platforms such as Dryad, GitHub, and Docker facilitate data, code, and environment management, they do not inherently guarantee the reproducibility of results, with issues like data incompleteness, forgotten parameters, or software discrepancies posing additional challenges. To address these critical gaps, we developed a BioMedical data Analysis Platform (BMAP) to offer online and localized categorized management of research assets. BMAP enhances workflow efficiency by transforming complex pipelines into user-friendly web applications, promoting consistency and standardization across team analyses. Its comprehensive web analysis module and seamless integration with data and computing resources support automated result reproducibility and visualization. According to the assessment, 1,692 omics-related figures from 101 recent articles, across 45 visualization types, were tested with BMAP, which could cover 37.8% of the types and 64.3% of the figures. BMAP also enables the sharing and enhancement of research methods through its cloud platform, allowing researchers to utilize the previously developed and validated tools, thereby reducing redundant effort and minimizing analytical discrepancies due to methodological differences.

bioinformatics↗

bioRxiv2024

Representation of visual uniformity in the lateral prefrontal cortex

Visual illusions tend to have early visual cortical correlates. However, this general trend may not apply to our subjective impression of a detailed and uniform visual world, which may be considered illusory given the paucity of peripheral processing. Using a psychophysically calibrated visual illusion, we assessed the patterns of hemodynamic activity in the human brain that distinguished between the illusory percept of uniformity in the periphery (i.e., Gabor patches having identical orientations) from the accurate perception of incoherence. We identified voxel patterns in the lateral prefrontal cortex that predicted perceived uniformity, which could also generalize to scene uniformity in naturalistic movies. Because similar representations of visual uniformity can also be found in the intermediate and late layers of a feedforward convolutional neural network, the perception of uniformity may involve high-level coding of abstract properties of the entire scene as a whole, that is distinct from the filling-in of specific details in early visual areas.

neuroscience↗

bioRxiv2024

A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex

Sensory experience drives the refinement and maturation of neural circuits during postnatal brain development through molecular mechanisms that remain to be fully elucidated. One likely mechanism involves the sensory-dependent expression of genes that encode direct mediators of circuit remodeling within developing cells. However, while studies in adult systems have begun to uncover crucial roles for sensory-induced genes in modifying circuit connectivity, the gene programs induced by brain cells in response to sensory experience during development remain to be fully characterized. Here, we present a single-nucleus RNA-sequencing dataset describing the transcriptional responses of cells in mouse visual cortex to sensory deprivation or sensory stimulation during a developmental window when visual input is necessary for circuit refinement. We sequenced 118,529 individual nuclei across sixteen neuronal and non-neuronal cortical cell types isolated from control, sensory deprived, and sensory stimulated mice, identifying 1,268 unique sensory-induced genes within the developing brain. To demonstrate the utility of this resource, we compared the architecture and ontology of sensory-induced gene programs between cell types, annotated transcriptional induction and repression events based upon RNA velocity, and discovered Neurexin and Neuregulin signaling networks that underlie cell-cell interactions via CellChat. We find that excitatory neurons, especially layer 2/3 pyramidal neurons, are highly sensitive to sensory stimulation, and that the sensory-induced genes in these cells are poised to strengthen synapse-to-nucleus crosstalk by heightening protein serine/threonine kinase activity. Altogether, we expect this dataset to significantly broaden our understanding of the molecular mechanisms through which sensory experience shapes neural circuit wiring in the developing brain.

neuroscience↗

bioRxiv2024

Human birth tissue products as a regenerative medicine to inhibit post-surgical pain through multi-modal action

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain. Local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO-induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain. Moreover, we unravel the underlying mechanisms of pain inhibition induced by FLO and HC-HA/PTX3.

neuroscience↗