Biology subjects

Vo, N.

Publications and source records attributed to Vo, N..

10 recordsLinked to original sources

bioRxiv2026

Angiopoietin-like protein 7 (ANGPTL7)-mediated effects on resident immune cells contribute to neurodegeneration in glaucomatous optic nerve head

Glaucoma is an optic neuropathy characterized by progressive retinal degeneration. Population genetic analyses describe an association of variants in angiopoietin-like protein 7 (ANGPTL7) with lower intraocular pressure (IOP) and decreased glaucoma susceptibility. In addition to its reported role in the trabecular meshwork (TM), we demonstrate that ANGPTL7 is also expressed within disease-relevant cell types of the human posterior eye, specifically prelaminar optic nerve head astrocytes (ONHA). Contrasting with previously published findings, we observe no difference in IOP between Angptl7-/- mice and wild-type littermates. Despite absence of an IOP phenotype, loss of ANGPTL7 protects from IOPinduced retinal ganglion cell (RGC) damage in a rodent glaucoma neurodegeneration model. ANGPTL7 may signal through LAIR1-positive immune cells, potentially contributing to pro-inflammatory signaling and phenotypic modulation of resident immune cells, with evidence suggesting that oligomerization of ANGPTL7 is necessary for its activity. Comprehensively, our data highlight an unappreciated role of ANGPTL7 in modulating neuroinflammation in the posterior eye, contributing to glaucoma progression.

neuroscience↗

bioRxiv2025

CD33-CD45 Interaction Reveals a Mechanistic Link to Alzheimer's Disease Susceptibility

The innate immune gene CD33, encoding a myeloid inhibitory sialic acid-binding receptor, is associated with Alzheimers disease (AD) susceptibility. The AD-associated rs3865444CC risk variant reduces splicing of the sialic acid-binding domain and increases expression of the full-length (sialic acid-binding) CD33 isoform seven-fold compared to the rs3865444AA protective genotype. Here we identify CD45 as an immune cell-specific sialic acid-dependent cis CD33 binding partner, whose phosphatase activity is inhibited by CD33. Overexpression of CD33 or loss of CD45 contributes to impaired microglial clearance of amyloid beta and amyloid beta-induced loss of dendritic spines in microglial-neuronal co-cultures, aligning with a detrimental effect of CD33-mediated inhibition of CD45. CD33-CD45 interaction frequency was increased in monocytes from individuals with the rs3865444CC risk variant compared to rs3865444AA, as well as in AD compared to controls, independent of genotype. Furthermore, an interaction between CD33 and PTPRC (encoding CD45) gene expression in human brain tissue was associated with a pathological diagnosis of AD and global burden of AD pathology. Our findings thus establish a functional interaction between CD33 and CD45 relevant to AD susceptibility and systemic myeloid dysfunction in this disease.

neuroscience↗

bioRxiv2025

Identification of cellular and molecular risk signatures for progression to late-stage age-related macular degeneration using the 9-step Minnesota Grading System

Age-related macular degeneration (AMD) is a complex multifactorial disease, and the molecular mechanisms underpinning the progression of intermediate AMD to geographic atrophy are not fully understood. To better understand mechanisms driving progression, we performed bulk RNA sequencing on dissected macular and peripheral RPE/choroid and neural retina tissue from postmortem human eyes graded using the 9-step Minnesota Grading System (MGS). Binning of intermediate AMD cases into three distinct groups (AMD3L, AMD3M, AMD3H) based on the 5-year risk of progression enabled identification of distinct gene and pathway changes associated with progression to late-stage disease. Identified changes in gene expression were validated using ELISA or histological methods. RPE-specific genes and lipid metabolic pathways showed a transient increase in AMD3L followed by a pronounced decrease in AMD3H. In AMD3H, immune response genes such as C3, TREM2, and OLR1 were upregulated when compared to AMD3L samples, as well as genes specific to Muller glia/astrocytes (NGFR, SPP1, GPX3). Our findings support complement inhibition as a promising therapeutic option for slowing conversion to advanced AMD and identify macrophage and Muller/astrocyte genes as potential cell types to target in AMD. Further, we demonstrate the value of combining emerging, outcomes-based, clinically relevant grading systems with profiling technologies to generate new insights into ocular diseases. HighlightsO_LIIntermediate AMD (AMD3) can be further divided into 3 stages - AMD3L (low risk), AMD3M (intermediate risk), AMD3H (high risk) - using the MGS9 grading system based on the risk of disease progression to late AMD. C_LIO_LIRNA sequencing of the macular RPE/choroid shows opposing changes in gene expression of multiple biological pathways for both RPE and immune cells between AMD3L and AMD3H stages. C_LIO_LIIn the macular neural retina, most biological pathways were downregulated in AMD2 (early AMD) but upregulated in AMD4 (late AMD) compared to AMD1 (non-AMD control). C_LIO_LIMolecular and cellular signatures associated with a high risk of progression to AMD4 include activation of complement C3, two subtypes of macrophages expressing either TREM2 or OLR1, and Muller glia/astrocytes as evidenced by the upregulation of GFAP and NGFR. C_LIO_LIUnderstanding the roles of these high-risk associated genes in AMD progression will facilitate the development of new treatments that prevent or delay the irreversible central vision loss in AMD patients. C_LI

neuroscience↗

bioRxiv2025

Decoding menopause-induced tissue fibrosis using pan-tissue network inference

Menopause drives fibrotic remodeling and consequent tissue dysfunction across multiple organs, yet the tissue-conserved versus tissue-specific mechanisms underlying this phenomenon remain poorly defined. Here, we employed a network inference framework to uncover how menopause triggers coordinated shifts in intercellular signaling cascades that promote fibrosis. We leveraged publicly archived single-cell RNA-sequencing data from the liver, lung, pancreas, and skeletal muscle of ovariectomized and control mice. Given the central role of immune cells in orchestrating inflammation and fibrosis, we focused our analysis on immune cell populations. Using canonical markers of immune cells, we annotated major cell types and reconstructed cell-cell interaction networks to map transcriptional responses to hormonal shifts. Network analysis revealed pervasive reshaping of intercellular signaling common to all tissues evaluated in the setting of menopause. Within this immune-centered framework, we found that estrogen-responsive macrophages consistently function as major signaling hubs across all tissues evaluated, exhibiting extensive interactions with myofibroblasts--key drivers of extracellular matrix production and fibrotic remodeling. Notably, these shared signaling patterns were not detectable using conventional differential gene expression analysis, which revealed minimal overlap in gene-level responses in macrophages across tissues. In addition to conserved patterns, we identified tissue-specific interaction networks that reflect unique immune adaptations to hormonal loss. As an example, natural killer cells acted as a signaling hub in muscle-specific patterns, suggesting their direct contribution to menopausal skeletal muscle adaptation. Tissue-specific patterning was also evident in the liver, lung, and pancreas, where other immune cell types, such as CD8+ T cells and endothelial cells, functioned as prominent signaling hubs, indicating diverse remodeling of the immune microenvironment. The network approach introduced here represents a systems-level framework for mapping multicellular network rewiring following hormonal depletion and highlights conserved immune-stromal modules as potential therapeutic targets to prevent menopause-associated dysfunction.

systems biology↗

bioRxiv2024

Proteomic profile analysis of plasma and aqueous humor from glaucoma and non-glaucomatous patients

PurposeGlaucoma, a multifactorial ocular neuropathy, can lead to irreversible vision loss. Diagnosis involves assessing optic cupping (increased cup-to-disc ratios) and structural changes (like retinal nerve fiber layer thinning) through clinical imaging. Elevated intraocular pressure (IOP) is commonly associated with glaucoma, but not always. However, understanding disease progression is hindered by limited access to donor ocular tissue and consistent clinical data. We hypothesize that the proteome of aqueous humor and plasma may be altered in disease and correlates with clinical parameters such as IOP and cup-to-disc ratios. MethodsAqueous humor (AH) and plasma samples were collected from 36 glaucoma patients (17 male, 19 female), and 35 non-glaucomatous control patients (16 male, 19 female) undergoing cataract surgery. The protein profile was compared using the SOMAscan(R) assay system for proteome profiling. From glaucomatous donors, correlations between IOP and cup- to-disc ratios to proteome differences were determined. ResultsOverall proteomics profiles between both AH and plasma were compared by combining all samples (glaucoma and non-glaucoma) and then performing correlation analyses. This study revealed similar protein abundance in the two biological fluids. Additionally, it identified different abundance of proteins in plasma and AH between glaucoma and non- glaucoma samples. The differential proteins identified were involved in pathways related to vascular integrity, inflammation, immune response, cell adhesion, and complement activation. Generally, glaucomatous AH showed higher protein levels. Neurofilament light chain (NEFL) protein correlated with elevated IOP and inflammatory markers, but not with cup-to-disc ratios. ConclusionsTogether, our data demonstrate that the proteins identified in this study from glaucomatous donors correspond to markers of neurodegeneration and those that may inhibit cell proliferation or disrupt vascular integrity.

cell biology↗

bioRxiv2022

Macrophages regulate gastrointestinal motility through complement component 1q

Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for immune defense of the intestine. Instead, C1q-expressing macrophages were localized to the intestinal submucosal plexus where they closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased peristaltic activity, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.

immunology↗

bioRxiv2021

Unique Microglial Transcriptomic Signature within the Hippocampal Neurogenic Niche

Microglia, the resident immune cells of the brain, are crucial in the development of the nervous system. Recent evidence demonstrates that microglia modulate adult hippocampal neurogenesis by inhibiting cell proliferation of neural precursors and survival both in vitro and in vivo, thus maintaining a balance between cell division and cell death in the neural stem cell pool. There are increasing reports suggesting these microglia found in neurogenic niches differ from their counterparts in non-neurogenic areas. Here, we present evidence that microglia in the hippocampal neurogenic niche are a specialized population that express genes known to regulate neurogenesis. By comprehensively profiling myeloid lineage cells in the hippocampus using single cell RNA-sequencing, we resolve transcriptomic differences in microglia originating from the subgranular zone. These cells have lower expression of genes associated with homeostatic microglia and increased expression of genes associated with phagocytosis. Intriguingly, this small yet distinct population expresses a gene signature with substantial overlap with previously characterized phenotypes, including disease associated microglia (DAM), a particularly unique and compelling microglial state.

cell biology↗

bioRxiv2021

X-ray induced bio-acoustic emissions from cultured cells

PurposeWe characterise for the first time the emission of bio-acoustic waves from cultured cells irradiated at doses of X-ray photon radiation relevant to medical and accidental exposure. Methods and materialsHuman cancer cell lines (MCF-7, HL-60) and control cell-free media were exposed to 1 Gy X-ray photons while recording the sound generated before, during and after irradiation. Cellular cytotoxicity following photon irradiation was determined by extracellular LDH levels, and irradiated cell conditioned media were tested for their ability to elicit a bystander effect in reporter cells. ResultsWe report the first recorded acoustic signals captured from a collective pressure wave response to ionising irradiation. The signature of the collective acoustic peaks was temporally wider and with higher acoustic power for irradiated HL-60 than for irradiated MCF-7. ConclusionsWe show that at doses of X-ray irradiation capable of producing the release of bystander effect-inducing activity, both cell types emit a characteristic acoustic signal for the duration of the radiation pulse. The rapid signal decay is consistent with a passive rather than an active acoustic signal generation. This preliminary study suggests that further work on the potential role of radiation induced acoustic emission (RIAE) in the cellular bystander effect is merited.

cell biology↗

bioRxiv2020

Computationally-efficient spatiotemporal correlation analysis super-resolves anomalous diffusion

Anomalous diffusion dynamics in confined nanoenvironments govern the macroscale properties and interactions of many biophysical and material systems. Currently, it is difficult to quantitatively link the nanoscale structure of porous media to anomalous diffusion within them. Fluorescence correlation spectroscopy super-resolution optical fluctuation imaging (fcsSOFI) has been shown to extract nanoscale structure and Brownian diffusion dynamics within gels, liquid crystals, and polymers, but has limitations which hinder its wider application to more diverse, biophysically-relevant datasets. Here, we parallelize the least-squares curve fitting step on a GPU improving computation times by up to a factor of 40, implement anomalous diffusion and two-component Brownian diffusion models, and make fcsSOFI more accessible by packaging it in a user-friendly GUI. We apply fcsSOFI to simulations of the protein fibrinogen diffusing in polyacrylamide of varying matrix densities and super-resolve locations where slower, anomalous diffusion occurs within smaller, confined pores. The improvements to fcsSOFI in speed, scope, and usability will allow for the wider adoption of super-resolution correlation analysis to diverse research topics.

biophysics↗

bioRxiv2019

An evaluation of Nephrology Literature for Transparency and Reproducibility Indicators: Cross-sectional Review

BackgroundReproducibility is critical to diagnostic accuracy and treatment implementation. Concurrent with clinical reproducibility, research reproducibility establishes whether the use of identical study materials and methodologies in replication efforts permit researchers to arrive at similar results and conclusions. In this study, we address this gap by evaluating nephrology literature for common indicators of transparent and reproducible research.\n\nMethodsWe searched the National Library of Medicine catalog to identify 36 MEDLINE-indexed, English language nephrology journals. We randomly sampled 300 publications published between January 1, 2014, and December 31, 2018. In a duplicated and blinded fashion, two investigators screened and extracted data from the 300 publications.\n\nResultsOur search yielded 28,835 publications, of which we randomly sampled 300 publications. Of the 300 publications, 152 (50.67%) were publicly available whereas 143 (47.67%) were restricted through paywall and 5 (1.67%) were inaccessible. Of the remaining 295 publications, 123 were excluded because they lack empirical data necessary for reproducibility. Of the 172 publications with empirical data, 43 (25%) reported data availability statements, 4 (2.33%) analysis scripts, 4 (2.33%) links to a protocol, and 10 (5.81%) were pre-registered.\n\nConclusionOur study found that reproducible and transparent research practices are infrequently employed by the nephrology research community. Greater efforts should be made by both funders and journals, two entities that have the greatest ability to influence change. In doing so, an open science culture may eventually become the norm rather than the exception.

bioinformatics↗