Biology subjects

Chen, H.-J.

Publications and source records attributed to Chen, H.-J..

At least 19 recordsLinked to original sources

bioRxiv2026

Nuclear Receptor Liver Receptor Homolog-1 drives Intestinal Stem Cell regeneration and UPR/ER stress response after gut injury

Stem cell renewal and crypt survival are tightly controlled processes critical for gut repair. Defining key regulators of intestinal healing is critical for the development of new epithelial-targeted therapies. We previously showed that the nuclear receptor LRH-1 (NR5A2) maintains intestinal epithelial health and protects against inflammatory damage. Here, using lineage tracing and selective LRH-1 knockout in the Atoh1+ secretory lineage we show LRH-1 is vital for intestinal stem cell (ISC) regeneration in complementary in vivo and ex vivo injury-recovery models. Transcriptomic profiling and pathway analysis reveal downregulation of ER stress and unfolded protein response (UPR) programs. Using a new in vivo model to ascertain how LRH-1 directly impacts intestinal cell responses, we identify key ER stress response genes Ire1 and Xbp1 as potential LRH-1 targets. Together our results uncover a novel mechanism whereby LRH-1 sustains the IRE1-XBP1 arm of the UPR to support injury-induced dedifferentiation and ISC regeneration. Our findings highlight LRH-1 as a promising therapeutic target for restoring epithelial integrity in inflammatory intestinal disorders.

cell biology↗

bioRxiv2026

Signal triangulation coordinates cell fate decisions in the developing jaw

Development of the vertebrate lower jaw depends on spatially precise cell fate decisions by cranial neural crest-derived cells (CNCCs) of the mandibular arch. From closer to the mouth (oral) to farther away (aboral), CNCCs adopt bone, cartilage, tendon, and stromal fates to shape the jaw skeleton and ensure proper connectivity to the musculature. How signaling pathways impact downstream transcriptional programs to generate distinct cell fates along the oral-aboral axis remains incompletely understood. Using photoconversion-based lineage tracing of CNCCs in zebrafish, we show that oral cells contribute to the lower jaw skeleton and aboral cells primarily to tendon, ligament, and stromal tissues. During embryogenesis, the oral domain is partitioned into lateral pitx1+ and medial foxf1+ subdomains distinct from an aboral nr5a2+, gsc+ domain. Using pharmacological inhibition and transgenic misexpression, we find that Bmp signaling establishes aboral nr5a2 and gsc expression, Fgf signaling oral-lateral pitx1 expression, and Hedgehog signaling oral-medial foxf1 expression. Analysis of mutants for pitx1, nr5a2, and gsc reveal that their oral-aboral expression domains are established independently of each other. We also identify enhancers regulating oral-aboral expression of pitx1 and nr5a2, with mutagenesis showing roles for Fgf-dependent ETS motifs in oral pitx1 and Bmp-dependent E-box motifs in aboral nr5a2 enhancer activity, consistent with dependence of nr5a2 expression on the Bmp-dependent E-box factor Hand2. These findings reveal how triangulation of three major signaling pathways converge on distinct gene regulatory modules to establish distinct oral-aboral cell fate decisions in the developing jaw.

developmental biology↗

bioRxiv2026

BMP antagonism is required for mandible outgrowth in zebrafish

The Meckels cartilage (MC) is a fundamental component of mandibular development across vertebrates. In mammals, MC is transient and functions primarily as an early template for mandibular ossification, whereas other vertebrates, including zebrafish, retain MC within the mandible throughout life. Despite its importance, the requirements for MC in sustaining mandibular growth and how signaling pathways implicated in MC development contribute to this process remain unclear. Here, we investigated the dosage-dependent roles of BMP antagonists during zebrafish MC development using mutant alleles of grem1a, nog2, and nog3. Compound mutant adults exhibited fully penetrant mandibular truncation. MC shortening emerged after early larval stages, indicating a requirement for BMP antagonism to sustain cartilage growth. Chondrocyte number remained unchanged as phenotypes developed, but mutants displayed disorganized cartilage morphology and increased chondrocyte volume. Molecular analyses revealed reduced col2a1a domains and expanded ihha and col10a1a expression, consistent with ectopic hypertrophic-like differentiation. Constitutive activation of BMP receptor signaling in chondrocytes recapitulated these phenotypes. Although osteogenesis appeared unaffected by 14 dpf, loss of a tnn skeletal mesenchyme population was observed. Together, these findings demonstrate that BMP antagonists sustain MC growth by regulating chondrocyte differentiation and cartilage organization to support mandibular growth in non-mammalian vertebrates. Summary StatementThis study leverages zebrafish to define the cellular and molecular mechanisms by which BMP antagonism sustains mandibular growth.

developmental biology↗

bioRxiv2026

Conserved cellular architecture and developmental mechanisms of the zebrafish

The meninges are a multilayered connective tissue that supports and protects the brain and skull, yet their developmental origins and signaling functions remain poorly understood. Here, we establish zebrafish as a tractable model for defining meningeal development and function across larval and adult stages. Using a restricted foxc1b:Gal4 reporter, we resolve the spatiotemporal emergence of meningeal fibroblasts and demonstrate a conserved, dosage-sensitive requirement for Foxc1 activity during meningeal formation. A targeted pharmacological screen identifies Wnt signaling as essential for timely establishment of the primary meninx. To define adult meningeal diversity, we integrate single-cell multiome profiling with spatial validation and identify multiple transcriptionally distinct populations organized into layered compartments, including pial, arachnoid, dural, and periosteal dura fibroblasts. Finally, inducible larval ablation of meningeal cells reveals limited regenerative capacity following widespread loss and leads to persistent defects in calvarial osteogenesis and brain architecture, including reduced osteoblast differentiation at bone fronts and disrupted tissue organization at sites lacking meningeal recovery. Together, these findings define key features of zebrafish meninges and provide a framework for dissecting meningeal development, regeneration, and meninges-dependent signaling in vivo. Summary StatementThis study uses zebrafish to show how the tissues surrounding the brain develop early and guide proper formation of both the brain and skull.

developmental biology↗

bioRxiv2025

Bacteriophages of the predominant coral symbiont Endozoicomonas: novel models for coral holobiont interactions

Phages are important symbionts in corals that modulate the community and functions of other symbiotic bacteria. Although phages infecting coral pathogens have been reported, no phage targeting beneficial microorganisms in corals has been isolated to date. From seawater near Acropora and Stylophora corals, we isolated the first bacteriophages (designated EmPhiA and EmPhiS) that infect Endozoicomonas montiporae CL-33, a model strain of the coral-prevalent and predominant Endozoicomonas bacteria. Electron microscopic observations of both phages showed Myovirus-like morphology and head sizes characteristic of jumbophages, with cryo-electron microscopy reveals long whiskers unprecedent in known phages. Genetically, these phages shared 99.21% genome similarity and are distant from known prokaryotic viruses, suggesting that they represent a novel viral species, which we name Encorevirus taiwanensis, in a novel family Encoreviridae. The small burst sizes of these phages (13.14 PFU/cell for EmPhiA and 21.4 PFU/cell for EmPhiS) potentially enable continuous coexistence of them with host bacteria within corals, making them putative core members of coral holobionts. Furthermore, host range test showed that EmPhiA and EmPhiS infect both Endozoicomonas bacteria isolated from stony and soft corals, implying their presence in a broad spectrum of host marine invertebrates. Using EmPhiS, we also investigated phage-bacterium interaction during its infection of E. montiporae CL-33. Interestingly, in addition to modulation of host cellular machinery, we found expression of several tellurium resistance proteins by EmPhiS during infection, which may provide the host additional stress resistance. These phages provide a novel model that will greatly advance our understanding of coral-Endozoicomonas-phage interactions.

microbiology↗

bioRxiv2025

Familial ALS/FTD-associated RNA-Binding deficient TDP-43 mutants cause neuronal and synaptic dysregulation in vitro

TDP-43 is an RNA-binding protein constituting the pathological inclusions observed in [~]95% of ALS and [~]50% of FTD patients. In ALS and FTD, TDP-43 mislocalises to the cytoplasm and forms insoluble, hyperphosphorylated and ubiquitinated aggregates that enhance cytotoxicity and contribute to neurodegeneration. Despite its primary role as an RNA/DNA-binding protein, how RNA-binding deficiencies contribute to disease onset and progression are little understood. Among many identified familial mutations in TDP-43 causing ALS/FTD, only two mutations cause an RNA-binding deficiency, K181E and K263E. In this study, we used CRISPR/Cas9 to knock-in the two disease-linked RNA-binding deficient mutations in SH-SY5Y cells, generating both homozygous and heterozygous versions of the mutant TDP-43 to investigate TDP-43-mediated neuronal disruption. Significant changes were identified in the transcriptomic profiles of these cells, in particular, between K181E homozygous and heterozygous cells, with the most affected genes involved in neuronal differentiation and synaptic pathways. This result was validated in cell studies where the neuronal differentiation efficiency and neurite morphology were compromised in TDP-43 cells compared to unmodified control. Interestingly, divergent neuronal regulation was observed in K181E-TDP-43 homozygous and heterozygous cells, suggesting a more complex signalling network associated with TDP-43 genotypes and expression level which warrants further study. Overall, our data using cell models expressing the ALS/FTD disease-causing RNA-binding deficient TDP-43 mutations at endogenous levels show a robust impact on transcriptomic profiles at the whole gene and transcript isoform level that compromise neuronal differentiation and processing, providing further insights on TDP-43-mediated neurodegeneration.

neuroscience↗

bioRxiv2025

Unusual Ecofunctional Traits of Endozoicomonas: A Pan-Genomic Perspective

BackgroundEndozoicomonas is a widely distributed genus of marine bacteria, associated with various marine organisms, and recognized for its ecological importance in host health, nutrient cycling, and disease dynamics. Despite its significance, genomic features of Endozoicomonas remain poorly characterized due to limited availability of high-quality genome assemblies. ResultsIn this study, we sequenced 5 novel Endozoicomonas strains and re-sequenced 1 known strain to improve genomic resolution. By integrating these 6 high-quality genomes with 31 others that were publicly available, we identified a distinct, coral-associated clade not recognized by the previous two-clade classification. Pan-genomic analysis revealed significant variation in genetic trait distribution among clades. Notably, Endozoicomonas lacks quorum sensing capabilities, suggesting resistance to quorum quenching mechanisms. It also lacks the ability to synthesize and transport vitamin B12, indicating that it is not a primary source of this nutrient for holobionts. A remarkable feature of Endozoicomonas is its abundance of giant proteins, ranging from 15 to 65 kbp. We identified 92 such proteins, which clustered into three major groups based on amino acid similarity, each associated with specialized functions, such as antimicrobial synthesis, exotoxin production, and cell adhesion. Additionally, we explored prophages and CRISPR-Cas systems. We found that Endozoicomonas acquired prophages from diverse sources via infection or other types of gene transfer. Notably, CRISPR-Cas sequences suggest independent evolutionary trajectories from both prophage acquisition and phylogenetic lineage, implying a potential influence of geographic or environmental pressures. ConclusionsThis study provides new insights into the genomic diversity of Endozoicomonas and its genetic adaptation to diverse hosts. Identification of novel genomic features, including deficiencies in B12 synthesis and quorum sensing, the presence of giant proteins, prophages, and CRISPR-Cas systems, underscores its ecological roles in various holobionts. These findings open new avenues for research on Endozoicomonas and its ecological interactions.

ecology↗

bioRxiv2024

Identification of novel small molecule chaperone activators for neurodegenerative disease treatment

A pathological hallmark of neurodegenerative disease is the accumulation of aberrant protein aggregates which contribute to the cytotoxicity and are therefore a target for new therapy development. One key machinery to manage cellular protein homeostasis is the chaperones proteins, the heat shock proteins (HSPs) which are known to target aberrant proteins including TDP-43, tau and amyloid and rescue neurodegeneration in various disease models. As an attempt to target HSP activation for neurodegeneration therapy, we develop a drug screening assay to search compounds that activate the master regulator of HSPs, the transcription factor heat shock factor 1 (HSF1). As HSF1 is bound by HSP90 which prevents its activation, we develop a NanoBRET assay, which allows us to monitor and quantify the HSF1-HSP90 interaction in living cells to screen for compounds disrupting this interaction and thereby releasing HSF1 for activation. After the assay was optimised and validated for its robustness and reliability, a two thousand compound library was screened which produced 10 hits including a couple of known HSP90 inhibitors. Follow-up functional study showed that one of the hit oxyphenbutazone (OPB) significantly reduces the accumulation of insoluble TDP-43 in a cell model, displaying no signs of stress or toxicity. Further works are needed to characterise the mode-of-action of OPB in HSF1 activation and aberrant protein reduction, and the physiological impact of OPB on TDP-43 needs to be examined in an in vivo model. However, this study demonstrates a viable strategy for new drug discovery in targeting aberrant proteins and identifies potential candidates for translation into neurodegenerative disease treatment.

molecular biology↗

bioRxiv2024

Transfer of IgG from Long COVID patients induces symptomology in mice

SARS-CoV-2 infections worldwide led to a surge in cases of Long COVID, a post-infectious syndrome. It has been hypothesized that autoantibodies play a crucial role in the development of Long COVID and other syndromes, such as fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, we tested this hypothesis by passively transferring total IgG from Long COVID patients to mice. Using Glial Fibrillary Acidic Protein (GFAP) and type-I interferon expression, we stratified patients into three Long COVID subgroups, each with unique plasma proteome signatures. Remarkably, IgG transfer from the two subgroups, which are characterized by higher plasma levels of neuronal proteins and leukocyte activation markers, induced pronounced and persistent sensory hypersensitivity with distinct kinetics. Conversely, IgG transfer from the third subgroup, which are characterized by enriched skeletal and cardiac muscle proteome profiles, reduced locomotor activity in mice without affecting their motor coordination. These findings demonstrate that transfer of IgG from Long COVID patients to mice replicates disease symptoms, underscoring IgGs causative role in Long COVID pathogenesis. This work proposes a murine model that mirrors Long COVIDs pathophysiological mechanisms, which may be used as a tool for screening and developing targeted therapeutics.

immunology↗

bioRxiv2024

Effects of local and landscape factors on paddy field arthropod diversity: from species to communities

Agricultural landscapes are dynamic mosaics where environmental conditions vary across spatial scales. Identifying the spatial scales of environmental variables relevant to biodiversity is therefore essential for safeguarding biodiversity and the ecosystem services they provide. Although species richness is a useful aggregate metric the captures the responses of biodiversity as a whole, few studies have examined how species-specific responses to environmental variables give rise to community-level patterns. Failure to account for the heterogeneity in species responses may undermine potential processes that structure biodiversity. In this study, we sampled paddy-field inhabiting arthropods across the first growing season and examined how local (organic farming, water depth, and crop height) and landscape factors (forest cover and connectivity) affect their abundance and distribution. We built a spatio-temporally explicit joint species distribution model (JSDM) to answer three main questions. 1) How do species differ in their response to local and landscapes factors. 2) Can trophic guild explain the variation in species responses to environmental covariates, and 3) How do species-specific responses scale-up to structure species richness at the community-level? Our results show that the mean importance of environmental covariates was low overall (mean R2 = 0.21), suggesting the prevalence of stochasticity in structuring species abundances. However, environmental importance varied substantially across species (highest R2 = 0.87 and lowest R2 = 0.01) and that trophic guild explained only approximately 15% of species responses, which indicates high idiosyncrasy in species responses both within and among guilds. At the community-level, we found that species richness responds negligibly to local factors while increasing with forest cover at the landscape scale. The importance of each environmental covariate was reflected by the variability of species responses. Lastly, we found no evidence of dispersal limitation in structuring species abundances. Taken together, our study suggests that many paddy field arthropods exhibit transient dynamics and that environmental effects are highly species-specific, even within the same trophic guild. Most importantly, our study highlights the need to understand biodiversity from the species level to understand the processes that structure them in dynamic mosaic landscapes.

ecology↗

bioRxiv2023

Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration

After traumatic injury, healing of mammalian ligaments is typically associated with fibrotic scarring as opposed to scar-free regeneration. In contrast, here we show that the ligament supporting the jaw joint of adult zebrafish is capable of rapid and complete scar-free healing. Following surgical transection of the jaw joint ligament, we observe breakdown of ligament tissue adjacent to the cut sites, expansion of mesenchymal tissue within the wound site, and then remodeling of extracellular matrix (ECM) to a normal ligament morphology. Lineage tracing of mature ligamentocytes following transection shows that they dedifferentiate, undergo cell cycle re-entry, and contribute to the regenerated ligament. Single-cell RNA sequencing of the regenerating ligament reveals dynamic expression of ECM genes in neural-crest-derived mesenchymal cells, as well as diverse immune cells expressing the endopeptidase-encoding gene legumain. Analysis of legumain mutant zebrafish shows a requirement for early ECM remodeling and efficient ligament regeneration. Our study establishes a new model of adult scar-free ligament regeneration and highlights roles of immune-mesenchyme cross-talk in ECM remodeling that initiates regeneration. HighlightsO_LIRapid regeneration of the jaw joint ligament in adult zebrafish C_LIO_LIDedifferentiation of mature ligamentocytes contributes to regeneration C_LIO_LIscRNAseq reveals dynamic ECM remodeling and immune activation during regeneration C_LIO_LIRequirement of Legumain for ECM remodeling and ligament healing C_LI

molecular biology↗

bioRxiv2022

Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19

Previously, we and others have shown that SARS-CoV-2 spike-specific IgG antibodies play a major role in disease severity in COVID-19 by triggering macrophage hyperactivation, disrupting endothelial barrier integrity, and inducing thrombus formation. This hyper-inflammation is dependent on high levels of anti-spike IgG with aberrant Fc tail glycosylation, leading to Fc{gamma} receptor hyper-activation. For development of immune-regulatory therapeutics, drug specificity is crucial to counteract excessive inflammation while simultaneously minimizing inhibition of antiviral immunity. We here developed an in vitro activation assay to screen for small molecule drugs that specifically counteract antibody-induced pathology. We identified that anti-spike induced inflammation is specifically blocked by small molecule inhibitors against SYK and PI3K. We identified SYK inhibitor entospletinib as the most promising candidate drug, which also counteracted anti-spike-induced endothelial dysfunction and thrombus formation. Moreover, entospletinib blocked inflammation by different SARS-CoV-2 variants of concern. Combined, these data identify entospletinib as a promising treatment for severe COVID-19. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/521247v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@edb3d5org.highwire.dtl.DTLVardef@1b99dd8org.highwire.dtl.DTLVardef@129ec7corg.highwire.dtl.DTLVardef@165000f_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2022

The BNT162b2 mRNA SARS-CoV-2 vaccine induces transient afucosylatedIgG1 in naive but not antigen-experienced vaccinees

The onset of severe SARS-CoV-2 infection is characterized by the presence of afucosylated IgG1 responses against the viral spike (S) protein, which can trigger exacerbated inflammatory responses. Here, we studied IgG glycosylation after BNT162b2 SARS-CoV-2 mRNA vaccination to explore whether vaccine-induced S protein expression on host cells also generates afucosylated IgG1 responses. SARS-CoV-2 naive individuals initially showed a transient afucosylated anti-S IgG1 response after the first dose, albeit to a lower extent than severely ill COVID-19 patients. In contrast, previously infected, antigen-experienced individuals had low afucosylation levels, which slightly increased after immunization. Afucosylation levels after the first dose correlated with low fucosyltransferase 8 (FUT8) expression levels in a defined plasma cell subset. Remarkably, IgG afucosylation levels after primary vaccination correlated significantly with IgG levels after the second dose. Further studies are needed to assess efficacy, inflammatory potential, and protective capacity of afucosylated IgG responses. One sentence summaryA transient afucosylated IgG response to the BNT162b2 mRNA vaccine was observed in naive but not in antigen-experienced individuals, which predicted antibody titers upon the second dose.

immunology↗

bioRxiv2021

Microbiome restructuring: dominant coral bacterium Endozoicomonas species display differential adaptive capabilities to environmental changes

Bacteria in the coral microbiome play a crucial role in determining coral health and fitness, and the coral host often restructures its microbiome composition in response to external factors. An important but often neglected factor determining this microbiome restructuring is the capacity of microbiome members to adapt to a new environment. To address this issue, we examined how the microbiome structure of Acropora muricata corals changed over 9 months following a reciprocal transplant experiment. Using a combination of metabarcoding, genomics, and comparative genomics approaches, we found that coral colonies separated by a small distance harbored different dominant Endozoicomonas related phylotypes belonging to two different species, including a novel species, Candidatus Endozoicomonas penghunesis 4G, whose chromosome level (complete) genome was also sequenced in this study. Furthermore, the two dominant Endozoicomonas species showed varied adaptation capabilities when coral colonies were transplanted in a new environment. The differential adaptation capabilities of dominant members of the microbiome can a) provide distinct advantages to coral hosts when subjected to changing environmental conditions and b) have positive implications for future reefs.

microbiology↗

bioRxiv2021

Lifelong single-cell profiling of cranial neural crest diversification

The cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. By retrogradely mapping the emergence of lineage-specific chromatin accessibility, we identify a wealth of candidate lineage-priming factors, including a Gata3 regulatory circuit for respiratory cell fates. Rather than multilineage potential being an intrinsic property of cranial neural crest, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse neural crest lineage potential. HighlightsO_LISingle-cell transcriptome and chromatin atlas of cranial neural crest C_LIO_LIProgressive emergence of region-specific cell fate competency C_LIO_LIChromatin accessibility mapping identifies candidate lineage regulators C_LIO_LIGata3 function linked to gill-specific respiratory program C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/456710v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@1c4ca91org.highwire.dtl.DTLVardef@cf0d10org.highwire.dtl.DTLVardef@162bfe9org.highwire.dtl.DTLVardef@2565fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2021

The prevalence, predominance, and metabolic potentials of Candidatus Prochlorobium terpiosii in the coral-killing sponge, Terpios hoshinota

Terpios hoshinota is a ferocious, space-competing sponge that kills a variety of stony corals by overgrowth. Outbreaks of this species have led to intense coral reef damage and declines in living corals on the square kilometer scale in many geographical locations. Our large-scale 16S rRNA gene survey across three oceans revealed that the core microbiome of T. hoshinota included operational taxonomic units (OTUs) related to Prochloron, Endozoicomonas, Pseudospirillum, SAR116, Magnetospira, and Ruegeria. A Prochloron- related OTU was the most dominant cyanobacterium in T. hoshinota in the western Pacific Ocean, South China Sea, and Indian Ocean. The complete metagenome-assembled genome of the Prochloron-related cyanobacterium and our pigment analysis revealed that this bacterium had phycobiliproteins and phycobilins and lacked chlorophyll b, inconsistent with the iconic definition of Prochloron. Furthermore, the phylogenetic analyses based on 16S rRNA genes and 120 single-copy genes demonstrated that the bacterium was phylogenetically distinct to Prochloron, strongly suggesting that it should be a sister taxon to Prochloron; we therefore proposed this symbiotic cyanobacterium as a novel species under a new genus: Candidatus Paraprochloron terpiosii. With the recovery of the complete genome, we characterized the metabolic potentials of the novel cyanobacterium in carbon and nitrogen cycling and proposed a model for the interaction between Ca. Pp. terpiosi LD05 and T. hoshinota. In addition, comparative genomics analysis revealed that Ca. Paraprochloron and Prochloron showed distinct features in transporter systems and DNA replication. ImportanceThe finding that one species predominates cyanobacteria in T. hoshinota from different geographic locations indicates that this sponge and Ca. Pp. terpiosi LD05 share a tight relationship. This study builds the foundation for T. hoshinotas microbiome and paves a way for understanding the ecosystem, invasion mechanism, and causes of outbreak of this coral-killing sponge. Also, the first Prochloron-related complete genome enables us to study this bacterium with molecular approaches in the future and broadens our knowledge of the evolution of symbiotic cyanobacteria.

ecology↗

bioRxiv2020

Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses

For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk. One sentence summaryAnti-Spike IgG promotes hyper-inflammation.

immunology↗

bioRxiv2019

A genomic view of coral-associated Prosthecochloris and a companion sulfate-reducing bacterium

Endolithic microbial symbionts in the coral skeleton may play a pivotal role in maintaining coral health. However, compared to aerobic microorganisms, research on the roles of endolithic anaerobic microorganisms and microbe-microbe interactions in the coral skeleton are still in their infancy. In our previous study, we showed that a group of coral-associated Prosthecochloris (CAP), a genus of anaerobic green sulfur bacteria, was dominant in the skeleton of the coral Isopora palifera. Though CAP is diverse, the 16S rRNA phylogeny presents it as a distinct clade separate from other free-living Prosthecochloris. In this study, we build on previous research and further characterize the genomic and metabolic traits of CAP by recovering two new near-complete CAP genomes--Candidatus Prosthecochloris isoporaea and Candidatus Prosthecochloris sp. N1--from coral Isopora palifera endolithic cultures. Genomic analysis revealed that these two CAP genomes have high genomic similarities compared with other Prosthecochloris and harbor several CAP-unique genes. Interestingly, different CAP species harbor various pigment synthesis and sulfur metabolism genes, indicating that individual CAPs can adapt to a diversity of coral microenvironments. A novel near-complete SRB genome--Candidatus Halodesulfovibrio lyudaonia--was also recovered from the same culture. The fact that CAP and various sulfate-reducing bacteria (SRB) co-exist in coral endolithic cultures and coral skeleton highlights the importance of SRB in the coral endolithic community. Based on functional genomic analysis of Ca. P. sp. N1 and Ca. H. lyudaonia, we also propose a syntrophic relationship between the SRB and CAP in the coral skeleton. ImportanceLittle is known about the ecological roles of endolithic microbes in the coral skeleton; one potential role is as a nutrient source for their coral hosts. Here, we identified a close ecological relationship between CAP and SRB. Recovering novel near-complete CAP and SRB genomes from endolithic cultures in this study enabled us to understand the genomic and metabolic features of anaerobic endolithic bacteria in coral skeletons. These results demonstrate that CAP members with similar functions in carbon, sulfur, and nitrogen metabolisms harbor different light-harvesting components, suggesting that CAP in the skeleton adapts to niches with different light intensities. Our study highlights the potential ecological roles of CAP and SRB in coral skeletons and paves the way for future investigations into how coral endolithic communities will respond to environmental changes.

microbiology↗