Biology subjects

Deng, Y.

Publications and source records attributed to Deng, Y..

At least 145 records · Page 8Linked to original sources

bioRxiv2024

Evaluation of the effects of ripening-related genes on fruit metabolites and the associated regulatory mechanisms in tomato

Fruit ripening, which is a complex process involving dynamic changes to metabolites, is controlled by multiple factors, including transcription factors (TFs). Several TFs are reportedly essential regulators of tomato fruit ripening. To evaluate the effects of specific TFs on metabolite accumulation during fruit ripening, CRISPR/Cas9-mediated mutagenesis was combined with metabolome and transcriptome analyses to explore regulatory mechanisms. Specifically, we generated various genetically engineered tomato lines that differed regarding metabolite contents and fruit colors. The metabolite and transcript profiles indicated that the selected TFs have distinct functions that control fruit metabolite contents, especially carotenoids and sugars. Our findings may provide new insights into the regulatory mechanisms governing tomato fruit ripening. Moreover, a mutation to ELONGATED HYPOCOTYL5 (HY5) increased the tomato fruit fructose and glucose contents by approximately 20% (relative to the wild-type levels). Our in vitro assay showed that HY5 can bind directly to the G-box cis-element in the SWEET12c promoter to activate expression, thereby modulating sugar transport. Our findings have clarified the mechanism regulating fruit metabolic networks, while also providing the theoretical basis for breeding horticultural crops that produce fruit with diverse flavors and colors.g

plant biology↗

bioRxiv2024

Lupus-associated innate receptors drive extrafollicular evolution of autoreactive B cells

In systemic lupus erythematosus, recent findings highlight the extrafollicular (EF) pathway as prominent origin of autoantibody-secreting cells (ASCs). CD21loCD11c+ B cells, associated with aging, infection, and autoimmunity, are contributors to autoreactive EF ASCs but have an obscure developmental trajectory. To study EF kinetics of autoreactive B cell in tissue, we adoptively transferred WT and gene knockout B cell populations into the 564Igi mice - an autoreactive host enriched with autoantigens and T cell help. Time-stamped analyses revealed TLR7 dependence in early escape of peripheral B cell tolerance and establishment of a pre-ASC division program. We propose CD21lo cells as precursors to EF ASCs due to their elevated TLR7 sensitivity and proliferative nature. Blocking receptor function reversed CD21 loss and reduced effector cell generation, portraying CD21 as a differentiation initiator and a possible target for autoreactive B cell suppression. Repertoire analysis further delineated proto-autoreactive B cell selection and receptor evolution toward self-reactivity. This work elucidates receptor and clonal dynamics in EF development of autoreactive B cells, and establishes modular, native systems to probe mechanisms of autoreactivity.

immunology↗

bioRxiv2024

HortGenome Search Engine, a universal genomic search engine for horticultural crops

Horticultural crops comprising fruit, vegetable, ornamental, beverage, medicinal and aromatic plants play essential roles in food security and human health, as well as landscaping. With the advances of sequencing technologies, genomes for hundreds of horticultural crops have been deciphered in recent years, providing a basis for understanding gene functions and regulatory networks and for the improvement of horticultural crops. However, these valuable genomic data are scattered in warehouses with various complex searching and displaying strategies, which increases learning and usage costs and makes comparative and functional genomic analyses across different horticultural crops very challenging. To this end, we have developed a lightweight universal search engine, HortGenome Search Engine (HSE; http://hort.moilab.net), which allows querying genes, functional annotations, protein domains, homologs, and other gene-related functional information of more than 400 horticultural crops. In addition, four commonly used tools, including BLAST, Batch Query, Enrichment analysis, and Synteny Viewer, have been developed for efficient mining and analysis of these genomic data.

bioinformatics↗

bioRxiv2023

Unveiling Elevated Spontaneous Mutation Rates in Phyllostachys edulis (Moso Bamboo) through Whole Genome Sequencing (WGS) and Investigating the Impact of Atmospheric and Room Temperature Plasma (ARTP) Induced Mutagenesis

Moso bamboo, recognized for its wide distribution and economic importance, encounters challenges in varietal enhancement due to its protracted sexual reproduction cycle. This study employed whole-genome resequencing to uncover spontaneous mutations in Moso bamboo and investigated mutagenesis using atmospheric and room temperature plasma (ARTP). Through the sequencing results, we identified the population of flowering bamboo as an asexual breeding line. Notably, the flowering Moso bamboo population, exclusively derived from asexual reproduction, exhibited a high spontaneous mutation rate (4.54 x 10-4 to 1.15 x 10-3/bp) during sexual reproduction, considering parental and cross-pollination effects. Genetic disparities between offspring and parents exhibited a bimodal distribution, indicating a substantial cross-pollination rate. ARTP mutagenesis increased structural variations in offspring, while changes in SNPs and INDELs were less pronounced. Sanger sequencing validated a gene subset, providing a foundation for spontaneous mutation rate investigation via whole-genome sequencing. These insights, particularly from mutagenized offspring sequencing, contribute to Moso bamboo breeding strategies. HighlightMoso bamboo breeding revolutionized--high spontaneous mutations in asexually derived flowering population. ARTP mutagenesis boosts structural variations, shaping innovative breeding approaches.

genetics↗

bioRxiv2023

HGNNPIP: A Hybrid Graph Neural Network framework for Protein-protein Interaction Prediction

A deep understanding of Protein-protein interactions (PPIs) can provide comprehensive insights into many biological functions, thereby facilitating drug target identification and novel therapeutic design. Recent developments in artificial intelligence (AI)-driven computational methods have enabled the discovery of previously uncharacterized PPIs from large-scale interactome datasets. Almost all existing machine learning methods rely on Subcellular Localization (SL) to construct balanced datasets based on positive interactions to achieve predictions. Despite high fitting accuracy, the generalization ability of these models is questionable. To solve this problem, we analyzed existing methods and found that the high false positives in these methods are due to the bias in data distribution caused by SL. Therefore, we proposed a new strategy for negative instance sampling in PPI prediction and developed a Hybrid Graph Neural Network framework for Protein-protein Interaction Prediction (HGNNPIP). The experimental results showed that HGNNPIP works well on six benchmark datasets. Comparison analysis demonstrated that our model outperformed the other four existing methods. We also used HGNNPIP to explore the molecular contacts involved in the rice-pathogen interaction system. In vivo experiments confirmed multiple regulations related to disease resistance in rice. In summary, this study provides new insights into establishing a computational framework for PPI prediction with high reliability.

bioinformatics↗

bioRxiv2023

ERLIN1 may be involved in DHRS1-induced Change in Lipid Droplet Morphology in HeLa Cell

Dehydrogenase/reductase (SDR family) member1, DHRS1, a member of the conserved short chain dehydrogenase/reductase (SDR) superfamily, has been identified in lipid droplets proteome of different cells and tissues. However, until now, little is known about the potential role of DHRS1 on the lipid droplet (LD). Here, we report that DHRS1 localized to the lipid droplet in Huh7 and HeLa cells and ectopic expression of DHRS1 in HeLa cell induced a significant change in the lipid droplet morphology resulting in nearly 2 fold increase both in lipid droplet size and total triacylglycerol level independent of oleic acid treatment. DHRS1 interacted with ERLIN1, a non-caveolae lipid raft-like domain marker, in HeLa cell and ERLIN1 deficient HeLa cells displayed no detectable change in LD morphology. Although ectopic expression of DHRS1-GFP fusion protein in ERLIN1 deficient HeLa cells resulted in fewer GFP-labeled ring structures relative to WT HeLa cell; thus suggesting that ERLIN1 may be involved in regulating DHRS1 protein turnover. Taken together, these data showed that DHRS1 localized to the LD and induced a significant change in LD morphology which may be regulated by ERLIN1.

cell biology↗

bioRxiv2023

Epstein Barr virus infection induces tissue-resident memory T cells in mucosal lymphoid tissues

Epstein Barr virus (EBV) contributes to around 2% of all tumors worldwide. Simultaneously, more than 90% of healthy human adults persistently carry EBV without clinical symptoms. In most EBV carriers it is thought that virus-induced tumorigenesis is prevented by cell-mediated immunity. Specifically, memory CD8+ T cells recognize EBV-infected cells during latent and lytic infection. Using a symptomatic primary infection model, similar to infectious mononucleosis (IM), we found EBV induced CD8+ tissue resident memory T cells (TRMs) in mice with a humanized immune system. These human TRMs were preferentially established after intranasal EBV infection in nasal-associated lymphoid tissues (NALT), equivalent to tonsils, the primary site of EBV infection in humans. They expressed canonical TRM markers, including CD69, CD103 and BLIMP-1, as well as Granzyme B, CD107a and CCL5, while demonstrating reduced CD27 expression and proliferation by Ki-67 expression. Despite cytotoxic activity and cytokine production ex vivo, these TRMs failed to control EBV viral loads in the NALT during infection although effector memory T cells (TEMs) controlled viral titers in spleen and blood. Overall, TRMs in mucosal lymphoid tissues are established by EBV infection, but primarily systemic CD8+ T cell expansion seems to attenuate viral loads in the context of IM-like infection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/565960v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1cc2a9borg.highwire.dtl.DTLVardef@1013ea1org.highwire.dtl.DTLVardef@b6be98org.highwire.dtl.DTLVardef@19af7c7_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

The impact of kit, environment and sampling contamination on the observed microbiome of bovine milk

Contaminants can easily outnumber bacteria that originate within the milk itself, milk microbiome research currently suffers from a critical knowledge gap; namely, does non-mastitis bovine milk contain a native microbiome? In this study, we sampled external and internal mammary epithelium, stripped and cisternal milk, used numerous negative controls to identify potential sources of microbial contamination. Two algorithms were used to mathematically remove this contamination and to track potential movement of microbes among our samples. Our results suggest that majority (i.e., >75%) of the sequence data generated from bovine milk and mammary epithelium samples represents contaminating DNA. The contaminants in milk samples were primarily sourced from the DNA extraction kits and the internal and external skin of the teat, while the teat canal and apex samples were mainly contaminated during the sampling process. After decontamination, the milk microbiome displayed a more dispersed, less diverse and compositionally distinct bacterial profile compared with the teat skin samples. Similar microbial compositions were observed between cisternal and stripped milk samples, as well as between teat apex and canal samples. Staphylococcus and Acinetobacter were the predominant genera detected in the sequences of milk samples, and bacterial culture showed growth of Staphylococcus and Corynebacterium spp. in 50% (7/14) of stripped milk samples and growth of Staphylococcus spp. in 7% (1/14) of cisternal milk samples. Our study suggests that microbiome data generated from milk samples obtained from clinically healthy bovine udders may be heavily biased by contaminants that enter the sample during the sample collection and processing workflows. ImportanceObtaining a non-contaminated sample of bovine milk is challenging due to the nature of the sampling environment and the route by which milk is typically extracted from the mammary gland. Furthermore, the very low bacterial biomass of bovine milk exacerbates the impacts of contaminant sequences in downstream analyses, which can lead to severe biases. Our finding showed that bovine milk contains very low bacterial biomass, and each contamination event (including sampling procedure and DNA extraction process) introduces bacteria and/or DNA fragments that easily outnumber the native bacterial cells. This finding has important implications for our ability to draw robust conclusions from milk microbiome data, especially if the data have not been subjected to rigorous decontamination procedures. Based on these findings, we strongly urge researchers to include numerous negative controls into their sampling and sample processing workflows; and to utilize several complementary methods for identifying potential contaminants within the resulting sequence data. These measures will improve the accuracy, reliability, reproducibility, and interpretability of milk microbiome data and research.

microbiology↗

bioRxiv2023

Vicious cycle of hemodynamic perturbation and endothelial injury in development and progression of pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) is a devastating disease caused by loss of effective lung microvasculature for which there is no curative treatment. Evidence from preclinical models and human disease-causing genetic mutations point to endothelial cell (EC) injury and apoptosis as a central trigger for the initiation of PAH. However, how EC apoptosis leads to pulmonary hypertension (PH) and complex arteriolar remodeling is uncertain. MethodsRats were subjected to SU5416-hypoxia (SUHx) and EC apoptosis, pulmonary vascular remodeling and arterial volume was assessed by immunohistochemistry, histology and microCT, respectively. Left pulmonary artery banding (LPAB) was performed, either 1 week before (prevention) or 5 weeks after SU injection (reversal), to study the effect of hemodynamic offloading. ResultsIn the SUHx model, EC apoptosis was markedly increased as early as 3 days post-SU, persisting through PAH development, and this was associated with a profound arterial pruning with reduction in lung arterial volume ([~]80%). LPAB abrogated lung EC apoptosis in the banded left lung and prevented as well as reversed arteriolar pruning. Moreover, in the reversal protocol, removal of the band at 10 weeks resulted in improvement in pulmonary hemodynamics and RV function at 13 weeks. ConclusionThese data demonstrate that perturbed hemodynamic factors triggered by lung microvascular arteriolar loss play a requisite role in perpetuating endothelial injury in experimental PAH, leading to persistent arterial EC injury and disease progression. Importantly, vascular loss, arterial remodeling and PH are reversible once the cycle of perturbed hemodynamics and EC injury is broken by unilateral lung banding.

physiology↗

bioRxiv2023

PhyGCN: Pre-trained Hypergraph Convolutional Neural Networks with Self-supervised Learning

Hypergraphs are powerful tools for modeling complex interactions across various domains, including biomedicine. However, learning meaningful node representations from hypergraphs remains a challenge. Existing supervised methods often lack generalizability, thereby limiting their real-world applications. We propose a new method, Pre-trained Hypergraph Convolutional Neural Networks with Self-supervised Learning (PhyGCN), which leverages hypergraph structure for self-supervision to enhance node representations. PhyGCN introduces a unique training strategy that integrates variable hyperedge sizes with self-supervised learning, enabling improved generalization to unseen data. Applications on multi-way chromatin interactions and polypharmacy side-effects demonstrate the effectiveness of PhyGCN. As a generic framework for high-order interaction datasets with abundant unlabeled data, PhyGCN holds strong potential for enhancing hypergraph node representations across various domains.

bioinformatics↗

bioRxiv2023

StableMate: a new statistical method to select stable predictors in omics data

Identifying statistical associations between biological variables is crucial to understand molecular mechanisms. Most association studies are based on correlation or linear regression analyses, but the identified associations often lack reproducibility and interpretability due to the complexity and variability of omics datasets, making it difficult to translate associations into meaningful biological hypotheses. We developed StableMate, a regression framework to address these challenges through a process of variable selection across heterogenous datasets. Given datasets from different environments, such as experimental batches, StableMate selects environment-agnostic (stable) and environment-specific predictors in predicting the response of interest. Stable predictors represent robust functional dependencies with the response, and can be used to build regression models that make generalizable prediction in unseen environments. We applied StableMate to 1) RNA-seq data of breast cancer to discover genes that consistently predict estrogen receptor expression across disease status, 2) metagenomics data to identify microbial signatures that show persistent association with colon cancer across study cohorts and 3) scRNA-seq data of glioblastoma to discern signature genes associated with development of pro-tumour microglia regardless of cell location. Our case studies demonstrate that StableMate is adaptable to regression and classification analyses and achieves comprehensive characterisation of biological systems for different omics data types.

bioinformatics↗

bioRxiv2023

Single cell optogenetics reveals attenuation-by-suppression in visual cortical neurons

The relationship between neurons input and spiking output is central to brain computation. Studies in vitro and in anesthetized animals suggest nonlinearities emerge in cells input-output (activation) functions as network activity increases, yet how neurons transform inputs in vivo has been unclear. Here, we characterize cortical principal neurons activation functions in awake mice using two-photon optogenetics. We deliver fixed inputs at the soma while neurons activity varies with sensory stimuli. We find responses to fixed optogenetic input are nearly unchanged as neurons are excited, reflecting a linear response regime above neurons resting point. In contrast, responses are dramatically attenuated by suppression. This attenuation is a powerful means to filter inputs arriving to suppressed cells, privileging other inputs arriving to excited neurons. These results have two major implications. First, somatic neural activation functions in vivo accord with the activation functions used in recent machine learning systems. Second, neurons IO functions can filter sensory inputs -- not only do sensory stimuli change neurons spiking outputs, but these changes also affect responses to input, attenuating responses to some inputs while leaving others unchanged. Significance statementHow neurons transform their inputs into outputs is a fundamental building block of brain computation. Past studies have measured neurons input-output (IO) functions in vitro or in anesthetized states. Here, we measure neurons IO functions in the awake and intact brain, where ongoing network activity can influence neurons responses to input. Using state-of-the-art optogenetic methods to deliver precise inputs to neurons near the cell body, or soma, we discover neurons have a supralinear-to-linear IO function, contrary to previous findings of threshold-linear, strongly saturating, or power law IO functions. This supralinear-to-linear somatic IO function shape allows neurons to decrease their responses to, or filter, inputs while they are suppressed below their resting firing rates, a computation we term attenuation-by-suppression.

neuroscience↗

bioRxiv2023

Functional connectome through the human life span

The lifespan growth of the functional connectome remains unknown. Here, we assemble task-free functional and structural magnetic resonance imaging data from 33,250 individuals aged 32 postmenstrual weeks to 80 years from 132 global sites. We report critical inflection points in the nonlinear growth curves of the global mean and variance of the connectome, peaking in the late fourth and late third decades of life, respectively. After constructing a fine-grained, lifespan-wide suite of system-level brain atlases, we show distinct maturation timelines for functional segregation within different systems. Lifespan growth of regional connectivity is organized along a primary-to-association cortical axis. These connectome-based normative models reveal substantial individual heterogeneities in functional brain networks in patients with autism spectrum disorder, major depressive disorder, and Alzheimers disease. These findings elucidate the lifespan evolution of the functional connectome and can serve as a normative reference for quantifying individual variation in development, aging, and neuropsychiatric disorders.

neuroscience↗

bioRxiv2023

Emergence of disease specific endothelial and stromal cell populations involved in arterial remodeling during development of pulmonary arterial hypertension

AbstractPulmonary arterial hypertension (PAH) is a severe and lethal pulmonary vascular disease characterized by arteriolar pruning and occlusive vascular remodeling leading to increased pulmonary vascular resistance and eventually right heart failure. While endothelial cell (EC) injury and apoptosis are known triggers for this disease, the mechanisms by which they lead to complex arterial remodeling remain obscure. We employed multiplexed single-cell RNA sequencing (scRNA-seq) at multiple timepoints during the onset and progression of disease in a model of severe PAH to identify mechanisms involved in the development of occlusive arterial lesions. There was significant loss of arterial volume as early as 1-week by microCT, preceding any evidence of occlusive arteriopathy, consistent with early arteriolar dropout. Maximal arterial pruning was seen by 5 to 8 weeks, with signs of progressive occlusive remodeling. Analysis of the scRNA-seq data resolved 44 lung cell populations, with widespread early transcriptomic changes at 1 week affecting endothelial, stromal and immune cell populations. Notably, this included emergence of a relatively dedifferentiated (dD) EC population that was enriched for Cd74 expression compared to general capillary (gCap) ECs which were primed to undergo endothelial-mesenchymal transition, as evidenced by RNA velocity analysis. However, at late timepoints (5 and 8 weeks), activated arterial ECs (aAECs) were the only cell population exhibiting persistent differential gene expression. This was characterized by a growth regulated state, including high expression of Tm4sf1, a gene implicated in cancer cell growth, which was also expressed by a smooth muscle (SM)-like pericyte cluster. Both these populations were localized to regions of arterial remodeling in the rat model and PAH patients, with aAECs contributing to intimal occlusive lesions and SM-like pericytes forming bands of medial muscularization. Together these findings implicate disease-specific vascular cells in PAH progression and suggest that TM4SF1 may be a novel therapeutic target for arterial remodeling.

molecular biology↗

bioRxiv2023

Ras-mediated homeostatic control of front-back signaling dictates cell polarity

Studies in the model systems, Dictyostelium amoebae and HL-60 neutrophils, have shown that local Ras activity directly regulates cell motility or polarity. Localized Ras activation on the membrane is spatiotemporally regulated by its activators, RasGEFs, and inhibitors, RasGAPs, which might be expected to create a stable front and back, respectively, in migrating cells. Focusing on C2GAPB in amoebae and RASAL3 in neutrophils, we investigated how Ras activity along the cortex controls polarity. Since existing gene knockout and overexpression studies can be circumvented, we chose optogenetic approaches to assess the immediate, local effects of these Ras regulators on the cell cortex. In both cellular systems, optically targeting the respective RasGAPs to the cell front extinguished existing protrusions and changed the direction of migration, as might be expected. However, when the expression of C2GAPB was induced globally, amoebae polarized within hours. Furthermore, within minutes of globally recruiting either C2GAPB in amoebae or RASAL3 in neutrophils, each cell type polarized and moved more rapidly. Targeting the RasGAPs to the cell backs exaggerated these effects on migration and polarity. Overall, in both cell types, RasGAP-mediated polarization was brought about by increased actomyosin contractility at the back and sustained, localized F-actin polymerization at the front. These experimental results were accurately captured by computational simulations in which Ras levels control front and back feedback loops. The discovery that context-dependent Ras activity on the cell cortex has counterintuitive, unanticipated effects on cell polarity can have important implications for future drug-design strategies targeting oncogenic Ras.

cell biology↗

bioRxiv2023

Genome analyses reveal the secondary metabolites potentially influence the geographical distribution of Fusarium pseudograminearum populations

Fusarium crown rot (FCR), caused by Fusarium pseudograminearum, significantly impacts wheat yield and quality in Chinas Huanghuai region. The rapid F. pseudograminearum epidemic and FCR outbreak within a decade remain unexplained. In this study, two high-quality, chromosome-level genomes of F. pseudograminearum strains producing 3-acetyl-deoxynivalenol (3AcDON) and 15-acetyl-deoxynivalenol (15AcDON) toxins were assembled. Additionally, 38 related strains were resequenced. Genomic differences such as single nucleotide polymorphisms (SNPs), insertions/deletions (indels), and structural variations (SVs) among F. pseudograminearum strains were analyzed. The whole-genome SNP locus based population classification mirrored the toxin chenotype (3AcDON and 15AcDON)-based classification, indicating the presence of genes associated with the trichothecene toxin gene cluster. Further analysis of differential SNP, indel, and SV loci between the 3AcDON and 15AcDON populations revealed a predominant connection to secondary metabolite synthesis genes. Notably, the majority of the secondary metabolite biosynthesis gene cluster (SMGC) loci were located in SNP-dense genomic regions, suggesting high mutability and a possible contribution to F. pseudograminearum population structure and environmental adaptability. This study provides insightful perspectives on the distribution and evolution of F. pseudograminearum, and for forecasting the spread of wheat FCR, thereby aiding in the development of preventive measures and control strategies.

microbiology↗

bioRxiv2023

sRNAfrag: A pipeline and suite of tools to analyze fragmentation in small RNA sequencing data

Fragments derived from small RNAs such as small nucleolar RNAs hold biological relevance. However, they remain poorly understood, calling for more comprehensive methods for analysis. We developed sRNAfrag, a standardized workflow and set of scripts to quantify and analyze sRNA fragmentation of any biotype. In a benchmark, it is able to detect loci of mature microRNAs fragmented from precursors and, utilizing multi-mapping events, the conserved 5 seed sequence of miRNAs which we believe may extraoplate to other small RNA fragments. The tool detected 1411 snoRNA fragment conservation events between 2/4 eukaryotic species, providing the opportunity to explore motifs and fragmentation patterns not only within species, but between. Availability: https://github.com/kenminsoo/sRNAfrag.

bioinformatics↗

bioRxiv2023

Single-cell RNA sequencing reveals characteristics of myeloid cells in pulmonary post-acute sequelae of SARS-CoV-2

BackgroundAlthough our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complication in COVID-19 infection remain unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequalae of SARS-CoV-2 infection with persistent pulmonary symptoms (PPASC). However, the dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown. ResultsTo characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from participants naive to SARS-CoV-2 (Control) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC). We analyzed more than 34,139 PBMCs by integrating our dataset with previously reported control datasets (GSM4509024) cell distribution. In total, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes and dendritic cells) was increased in PPASC compared to controls. MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis- related (VEGF, WNT, and SMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. In PPASC, we observed interactive VEGF ligand- receptor pairs among MLCs, and network modules in CD14+ (cluster 4) and CD16+ (Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID- 19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS- CoV-2 naive samples. ConclusionThis study offers valuable insights into the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests their potential role as a driver of PPASC.

microbiology↗