bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2022.07.03.498592

In-depth investigation of microRNA-mediated cross-kingdom regulation between Asian honey bee and microsporidian

Fan, X.·Zhang, W.·Zhang, K.·Zhang, J.·Long, Q.·Wu, Y.·Zhu, L.·Chen, D.·Guo, R.
View original source ↗Export metadata ↓

Abstract

Asian honey bee Apis cerana is the original host for Nosema ceranae, a unicellular fungal parasite that causes bee nosemosis throughout the world. Currently, interaction between A. cerana and N. ceranae is largely unknown. Here, based on our previously gained high-quality RNA-seq and small RNA-seq data from N. ceranae-infected A. c. cerana workers midguts and clean spores, differentially expressed mRNAs (DEmiRNAs) in N. ceranae targeted by DEmiRNAs in host midguts and A. c. cerana DEmRNAs targeted by microsporidian DEmiRNAs were predicted using bioinformatics, and then target DEmRNAs in microsporidian and host were annotated and investigated, with a focus on targets involved in N. ceranae glycolysis/glyconeogenesis and virulence factors as well as A. c. cerana energy mechanism and immune response. Its found that 97 down-regulated (60 up-regulated) mRNAs in NcCKM vs NcTM1 were potentially targeted by eight up-regulated (six down-regulated) miRNAs in AcCKMI1 vs AcTMI1, 44 down-regulated (15 up-regulated) mRNAs in NcCKM vs NcTM2 were putative targets of seven up-regulated (two down-regulated) miRNAs in AcCKMI2 vs AcTMI2. Additionally, miR-60-y and miR-676-y were found to up-regulate in AcCKMI1 vs AcTMI1 and target genes engaged in spore wall protein and glycolysis/gluconeogenesis, while miR-60-y in AcCKMI1 vs AcTMI1 was up-regulated and potentially targeted a glycolysis/gluconeogenesis-associated gene. Comparatively, 343 down-regulated (138 up-regulated) mRNAs in AcCKM1 vs AcTM1 were putative targets of 121 up-regulated (112 down-regulated) miRNAs in NcCKMI vs NcTMI1, 247 down-regulated (110 up-regulated) mRNAs were putatively targeted by 110 up-regulated (104 down-regulated) miRNAs in NcCKMI vs NcTMI2. Further analysis showed that 31 up-regulated miRNAs in NcCKMI vs NcTMI1 potentially targeted 12 down-regulated mRNAs in AcCKM1 vs AcTM1, which were involved in five immune-related pathways such as phagasome and Jak-STAT signaling pathway, whereas nine up-regulated miRNAs in NcCKMI vs NcTMI2 putatively targeted five down-regulated mRNAs in AcCKM2 vs AcTM2, which were engaged in three immune-related pathways including endocytosis, lysosomes, and regulation of autophagy. In addition, miR-21-x was observed to up-regulate in NcCKMI vs NcTMI1 and target a oxidative phosphorylation-related gene. Finally, potential targeting relationship between two host DEmiRNAs-microsporidian DEmRNAs pairs and two microsporidian DEmiRNAs-host DEmRNAs pairs were verified on basis of RT-qPCR. Our findings not only lay a foundation for exploring the molecular mechanism underlying cross-kingdom regulation between A. c. cerana workers and N. ceranae, but also offer valuable insights into Asian honey bee-microsporidian interaction.

Source connections

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Fan, X., Zhang, W., Zhang, K., Zhang, J., Long, Q., Wu, Y., Zhu, L., Chen, D., Guo, R.. 2022-07-03. In-depth investigation of microRNA-mediated cross-kingdom regulation between Asian honey bee and microsporidian. https://doi.org/10.1101/2022.07.03.498592

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗
bioRxiv2024

COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and resulting coronavirus disease (COVID-19) causes placental dysfunction, which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests that pathophysiology associated with maternal COVID-19, rather than direct placental infection, is responsible for placental dysfunction and alteration of the placental transcriptome. We hypothesized that maternal circulating extracellular vesicles (EVs), altered by COVID-19 during pregnancy, contribute to placental dysfunction. To examine this hypothesis, we characterized maternal circulating EVs from pregnancies complicated by COVID-19 and tested their effects on trophoblast cell physiology in vitro. We found that the gestational timing of COVID-19 is a major determinant of circulating EV function and cargo. In vitro trophoblast exposure to EVs isolated from patients with an active infection at the time of delivery, but not EVs isolated from Controls, altered key trophoblast functions including hormone production and invasion. Thus, circulating EVs from participants with an active infection, both symptomatic and asymptomatic cases, can disrupt vital trophoblast functions. EV cargo differed between participants with COVID-19 and Controls, which may contribute to the disruption of the placental transcriptome and morphology. Our findings show that COVID-19 can have effects throughout pregnancy on circulating EVs and circulating EVs are likely to participate in placental dysfunction induced by COVID-19.

pathology↗
bioRxiv2024

Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias

BackgroundIntramyocardial injection of human pluripotent stem cell-derived cardiomyocytes following a myocardial infarction (MI) improves cardiac function in large animal models, but associated ventricular arrhythmias are major safety concern. We hypothesized that transendocardial injection of human induced pluripotent stem cell (hiPSC)-derived committed cardiac progenitor cells (CCPs), combined with cardiac fibroblast-derived extracellular matrix (cECM) to enhance cell retention, will generate cardiac tissue grafts improving contractility without triggering ventricular arrhythmias. MethodshiPSCs were differentiated using bioreactors and small molecules to produce committed cardiac progenitor cells (CCPs). MI was created using a coronary artery balloon occlusion and reperfusion model in Yucatan mini pigs. Four weeks later, epicardial needle injections of CCPs+cECM were performed in a small initial feasibility cohort (n=6), and then transendocardial injections of CCPs+cECM (n=14), CCPs alone (n=14), cECM alone (n=4) or vehicle control (n=13) into the peri-infarct region in a randomized cohort. Arrhythmias were evaluated using implanted event recorders. Magnetic resonance imaging (MRI) and invasive pressure-volume assessment were used to evaluate left ventricular anatomic and functional performance. Detailed histology was performed to detect and characterize human grafts. ResultsA scalable biomanufacturing protocol was developed generating CCPs which can efficiently differentiate into cardiomyocytes or endothelial cells in vitro. Intramyocardial delivery of CCPs to post-MI porcine hearts resulted in engraftment and differentiation of CCPs to form ventricular cardiomyocyte rich grafts. There was no significant difference in cardiac MRI-based measured cardiac volumes or function between control, CCP and CCP+cECM groups; however, pressure-volume analysis showed an improvement in dobutamine-stimulated functional reserve in CCP and CCP+cECM groups. Delivery of CCPs did not result in tumors or ventricular arrhythmias. ConclusionsTransendocardial delivery of CCPs with or without cECM into post-MI porcine hearts resulted in comparable human cardiomyocyte grafts which did not improve resting LV function but did improve stress-induced contractile reserve without triggering ventricular arrhythmias.

pathology↗