Biology subjects

Huang, T.-C.

Publications and source records attributed to Huang, T.-C..

9 recordsLinked to original sources

bioRxiv2026

Seasonal population structure and adaptive signatures across long-term marine microbial time series

Long-term microbial population dynamics can reveal how ocean microbiomes respond to environmental variation, but resolving within-species change requires suitable genomic references. We integrated 30 PacBio HiFi long-read metagenome-assembled genomes (MAGs) from the northwestern Mediterranean Sea with monthly Illumina metagenomes from neighboring time series spanning 12 and 7 years. Population differentiation varied widely among genomes and often differed in magnitude between sites, while a subset showed increasing differentiation with temporal distance. Genetic diversity and population structure were frequently seasonal, with populations associated with warm or cold waters and others spanning both thermal regimes. Candidate adaptive genes accounted for 1.6-3.0% of coding sequences, and many were detected in both time series. Their pN/pS trajectories included regular seasonal fluctuations consistent with changing strain or ecotype contributions, alongside irregular temporal patterns. These results show that combining long-read MAG references with dense short-read time series can resolve seasonal population structure, site-specific differentiation, and candidate adaptive variation within marine microbial species, providing a framework for tracking contemporary population-genomic change in the ocean.

ecology↗

bioRxiv2026

Decadal signatures of seasonal and ENSO-driven selection in microbial populations in distant oceans

Despite the crucial role of the ocean microbiome for global ecosystem processes, its response to global change remains poorly understood. Global change will exert selection on microbial species through changes in the genetic composition of their populations, favouring strains that are better adapted to new conditions. Analyzing long-term genomic variation in microbial populations inhabiting climatically comparable but oceanographically distinct regions may provide insights into their responses to future environmental conditions. We analyzed coastal marine microbiomes from two distant long-term observatories with Mediterranean-type climates but contrasting oceanographic regimes: the Blanes Bay Microbial Observatory (BBMO; Northwestern Mediterranean Sea) and the Microbes in the Coastal Region of Orange County (MiCRO; California coast, Pacific Ocean). Sampling conducted at least monthly during 15 and 10 years, respectively, yielded 1,535 Metagenome-Assembled Genomes (MAGs) in BBMO and 1,068 MAGs plus 187 Single-Amplified Genomes (SAGs) in MiCRO. Among these, we found 250 genomes with intraspecific (>95% genome similarity) representatives occurring at both sites. In contrast, at the strain-level threshold ([≥]99% genome similarity), only 13 BBMO genomes matched 15 closely related representatives in MiCRO. As genome similarity increased, we observed a shift from cosmopolitan to more coastal distributions and a slight increase in genome size, pointing to niche adaptation. Across both time series, we observed widespread seasonal population structure, with most genomes (~70%) showing significant seasonal structuring of variant composition. Moreover, in MiCRO, ~76% of the tested genomes also showed El Nino Southern Oscillation (ENSO)-associated structure in variant composition beyond seasonal effects. Focusing on a Prochlorococcus genome with intraspecific representatives at both locations (>96% genome similarity) we further found recurrent seasonal mutations and non-synonymous to synonymous mutation ratios (pN/pS) from multiple genes, together with signatures of positive selection (higher pN/pS) coinciding with El Nino events in MiCRO. This suggests an imprint of ENSO in marine microbial populations. Thus, beyond seasonality, long-term climatic oscillations may shape microbial populations. This has implications for understanding how the ocean microbiome will respond to long-term environmental change and prolonged disturbances through population-level genomic variation.

microbiology↗

bioRxiv2025

Global re-organisation of genome architecture at the transition to gametogenesis

Global epigenetic resetting in the gonadal primordial germ cells (PGCs) enables transition from early PGCs to gametogenesis and eventual restoring of totipotency after fertilisation. This reprogramming process involves global DNA demethylation, changes in nuclear morphology as well as remodeling of repressive histone modifications. Here, using combined cytological and Hi-C based methods, we reveal that following the epigenetic reprogramming and concomitant with their commitment to gametogenesis, pre-meiotic gonadal germ cells are characterised by a unique chromosome and genome architecture. This involves separation of individual chromosomes and anchoring of centromeres at the nuclear periphery, reduction of inter-chromosome interactions and disentangling of chromosome ends. Furthermore, genome-wide contact mapping documents striking remodeling of 3D genome architecture across all observable levels including disruption of topological associating domains (TADs), loss of detectable loops and reduced active-active compartment interactions. We further show that the diminished TADs correlate with the reduced levels of CTCF thus providing a unique in vivo physiological model to understand genome folding principles. Finally, we show that primordial germ cell like cells (PGCLCs), derived from embryonic stem cells, do not exhibit the same chromatin organisation as embryonic germ cells suggesting that the 3D genome remodeling accompanies acquisition of meiotic competency. Collectively, our findings uncover the existence of a unique chromatin architecture in premeiotic male and female gonadal germ cells and document that alongside global DNA demethylation, the germline epigenetic reprogramming involves erasure of memory at the genome architectural level through a complete re-organisation of the 3D genome.

cell biology↗

bioRxiv2025

Interplay between Skin Sympathetic Nerve Activity and Gut Microbiota, the Neurocardiac Axis in Acute Coronary Syndrome

BACKGROUNDPrevious studies have linked gut dysbiosis to the acute coronary syndrome (ACS) and sympathetic nervous system disturbances. However, the relationship between skin sympathetic nerve activity (SKNA) and gut microbiota in ACS patients remains largely unexplored. We hypothesize that elevated SKNA may interact with specific microbial profiles in ACS. METHODS AND RESULTSFifteen ACS patients with age- and sex-matched controls were enrolled in the cross-sectional study. Subjects with type 2 diabetes or on antibiotics, proton pump inhibitors, or metformin were excluded. Demographic and clinical data were recorded, and SKNA was measured by neuECG. Gut microbial profiles were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Significant differences in alpha diversity, including Chao 1 index and Faiths phylogenetic diversity, were observed between the ACS and control groups (P<0.001). Distinct beta diversity between the two groups was also identified using unweighted normalized UniFrac analysis (P=0.001). Redundancy analysis and Mantel test revealed a significant relationship between SKNA and microbial profiles. Several butyrate-producing bacteria were decreased in the ACS group, while the genus Hungatella, a trimethylamine producer, showed a significant increase and was positively correlated with SKNA. Additionally, predicted microbial functional analysis indicated an elevation in branched-chain amino acid biosynthesis in the ACS group. CONCLUSIONSThis study is the first to establish an association between SKNA and gut microbial profiles in ACS patients. SKNA can serve as a biomarker for ACS, offering a simple and non-invasive tool to explore the interaction between the nervous system and gut microbiota in cardiovascular diseases. Clinical PerspectiveO_ST_ABSWHAT IS NEW?C_ST_ABSThe Skin sympathetic nerve activity (SKNA) is a novel and non-invasive recording of the sympathetic nervous system from the skin of patients. The NEW findings in our study from acute coronary syndrome (ACS) patients are (1) to establish the correlation between SKNA, heart rate variability and microbiota, (2) the Hungatella is correlated with SKNA and standard deviation of NN intervals (SDNN). WHAT ARE THE CLINICAL IMPLICATIONS?Since microbiota and sympathetic nervous system (SNS) might be essential factors of ACS, it is important to assess the abundance of microbiota and SNS activity for accurate management of ACS. The Hungatella, one of the microbiota involved in atherosclerotic cardiovascular disease, heart failure, inflammatory process, and anxiety disorder, might be the link between SNS and ACS. In our study, we prove the positive association between Hungatella and SKNA. Therefore, by checking the SKNA of patients with ACS, we might discover the SNS activity and also the underlying microbiota etiology of ACS. Then, it is critical and accurate to target Hungatella in ACS patients with high SKNA to reduce the risk of ACS.

microbiology↗

bioRxiv2024

Endophytic pyrroloquinoline quinone enhances banana growth and immunity against Fusarium wilt for plant-microbe mutualisms

Fusarium wilt has a substantial impact on global banana production, posing a threat to food security worldwide. However, breeding new Fusarium-resistant cultivars is difficult and time-consuming. Alternatively, endophytic biostimulants that could combat such pervasive plant diseases provide possible novel solutions. Our prior research demonstrated that a pyrroloquinoline quinone (PQQ)-producing endophytic bacterium, Burkholderia seminalis 869T2, can enhance the growth of various plant species and protect bananas from Fusarium wilt in the field. PQQ is a peptide-derived redox cofactor known to stimulate mitochondrial biogenesis and metabolism in animals, but its molecular roles, especially in plants, remain to be elucidated. In this study, multi-omics approaches were employed to explore the potential mechanisms through which PQQ influences banana plants. The result of in situ imaging mass spectrometry revealed that the endophytic metabolite PQQ does not function through direct antagonism against Fusarium. The follow-up transcriptomic profiling shows it could regulate plant respiration, TCA cycle, oxidative phosphorylation, NAD/NADP-dependent dehydrogenases, MAPK signalling, and various phytohormone signalling pathways. Furthermore, PQQ appeared to trigger plant systemic immunity, thereby enhancing plant health and resistance to biotic stress. Beyond that, the complete genome of 869T2 was determined for follow-up comparative genomics analyses, revealing its genetic contexts, potential evolutionary events of PQQ operons among the Burkholderia species, and the absence of human virulence-facilitating genes within those PQQ-producing agricultural isolates. In summary, this study facilitates our understanding of PQQ in plant-microbe mutualisms and provides scientific evidence for its future application in agriculture. Significance StatementFusarium wilt is caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), a notorious soil-borne pathogen that attacks bananas vascular system, which critically threatens global banana production and food security. A potential PQQ-producing endophytic strain has been confirmed to protect bananas through in planta biocontrol, reducing the morbidity of Banana Fusarium Wilt (BFW) disease in the field and promoting the growth of banana plants simultaneously. Our results revealed that the endophytic metabolite PQQ does not function through direct antagonism but triggers plant systemic immunity and coordinates energetic metabolisms, thereby improving the overall health of host plants and enhancing their resistance against Fusarium wilt.

plant biology↗

bioRxiv2024

AutoMorFi: Automated Whole-image Morphometry in Fiji/ImageJ for Diverse Image Analysis Needs

Running on the highly popular and accessible ImageJ/Fiji platform for biological image analysis, we have established AutoMorFi as a streamlined interface for automated whole-image morphometric analysis that generates at least 47 measurements per cell or object in under 1 minute. We performed multiple validated cluster and principal component analyses on nonredundant morphometric parameters derived from AutoMorFi for various cell types, objects, and organisms. We used images of rodent macrophages, human postmortem brain tissues from multiple sclerosis (MS) and Alzheimers disease (AD) patients, iPSC/animal models for Downs syndrome and autism spectrum disorder (ASD), and organisms such as sea anemone and corals. AutoMorFis adaptability extends across diverse imaging modalities including brightfield, confocal, or widefield fluorescence microscopy as well as underwater photography. Due to its unlimited and unbiased sampling across any image and high potential for modification and customization, using AutoMorFi has led to the discovery of new distinguishing features in previously studied cell types and organisms as well as the development of rapid diagnostic approaches. AutoMorFi represents a transformative tool that will accelerate morphometric analysis and offer broad relevance in biological studies.

cell biology↗

bioRxiv2023

A cyclic dipeptide for salinity stress alleviation and the trophic flexibility of an endophyte reveal niches in salt marsh plant-microbe interactions

In response to climate change, the nature of endophytes and their applications in sustainable agriculture has attracted the attention of academia and agro-industries. We focused on the endophytic halophiles of the endangered Taiwanese salt marsh plant, Bolboschoenus planiculmis, and evaluated the functions of the isolates through in planta salinity stress alleviation assay using Arabidopsis. An endophytic strain Priestia megaterium BP01R2 that could promote plant growth and salinity tolerance was further characterised through multi-omics approaches. The transcriptomics results suggested that BP01R2 could function by tuning hormone signal transduction, energy-producing metabolism, multiple stress responses, etc. In addition, a cyclodipeptide, cyclo(L-Ala-Gly), identified by metabolomics analysis was later confirmed to contribute to salinity stress alleviation in stressed plants by exogenous supplementation. Here we provide a new perspective on host-microbe interactions in the wetland biome based on the multi-omics investigation and mixotrophic character of BP01R2. This study revealed a biostimulant-based plant-endophyte symbiosis with potential application in sustainable agriculture and facilitated our understanding of those enigmatic cross-kingdom relationships.

microbiology↗

bioRxiv2020

Epigenetic therapy remodels the immune synaptic cytoskeleton to potentiate cancer susceptibility to γδ T cells

{gamma}{delta} T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune systems and can attack cancer or virus-infected cells in an MHC-unrestricted manner. Despite its antitumor ability in both autologous and allogeneic settings, earlier trials of adoptive {gamma}{delta} T cell transfer in solid tumors had limited success due to limitations in cell expansion and the lack of a strategy to modulate tumor lytic interactions between {gamma}{delta} T and cancer cells. Here, we show through quantitative surface proteomics and gene enrichment analyses that DNA methyltransferase inhibitors (DNMTis) upregulate multiple surface molecules related to {gamma}{delta} T cell activation in cancer cells. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded {gamma}{delta} T cells using a clinical-grade expansion protocol developed by our team to enrich for the V{delta}1 subset while preserving their antitumor effector functions. Mechanistically, DNMTis enhance immune synapse formation and stabilize the synaptic cleft to facilitate {gamma}{delta} T-mediated tumor lysis. Through integrated analysis of RNA-seq, DNA methylation, and ATAC-seq, we demonstrate that depletion of DNMTs induces coordinated pattern alterations of immune synaptic-cytoskeletal networks at the cancer side of the immune synapse. In addition, single-cell mass cytometry reveals enrichment of polyfunctional {gamma}{delta} T subsets by DNMTis. Combined DNMTi and adoptive {gamma}{delta} T transfer in a mouse lung cancer model offers a significant survival benefit. Consistently, the DNMTi-associated cytoskeleton signature identifies a subset of lung cancer patients with improved survival. Our results demonstrate that epigenetic mechanisms are crucial for cytoskeletal remodeling in cancer to potentiate immune attack and support a combinatorial strategy of DNMTis and {gamma}{delta} T cell-based immunotherapy in lung cancer management. One Sentence SummaryDNA methyltransferase inhibitors potentiate the killing of lung cancer by {gamma}{delta} T cells through remodeling cytoskeletal-immune synaptic networks.

cancer biology↗

bioRxiv2018

Signalling pathways drive heterogeneity of ground state pluripotency

Pluripotent stem cells (PSCs) can self-renew indefinitely while maintaining the ability to generate all cell types of the body. This plasticity is proposed to require heterogeneity in gene expression, driving a metastable state which may allow flexible cell fate choices. Contrary to this, naive PSC grown in fully defined 2i environmental conditions, containing small molecule inhibitors of MEK and GSK3 kinases, show homogenous pluripotency and lineage marker expression. However, here we show that 2i induces greater genome-wide heterogeneity than traditional serum-containing growth environments at the population level across both male and female PSCs. This heterogeneity is dynamic and reversible over time, consistent with a dynamic metastable equilibrium of the pluripotent state. We further show that the 2i environment causes increased heterogeneity in the calcium signalling pathway at both the population and single-cell level. Mechanistically, we identify loss of robustness regulators in the form of negative feedback to the upstream EGF receptor. Our findings advance the current understanding of the plastic nature of the pluripotent state and highlight the role of signalling pathways in the control of transcriptional heterogeneity. Furthermore, our results have critical implications for the current use of kinase inhibitors in the clinic, where inducing heterogeneity may increase the risk of cancer metastasis and drug resistance.

molecular biology↗