Biology subjects

Cho, C. H.

Publications and source records attributed to Cho, C. H..

11 recordsLinked to original sources

bioRxiv2026

Regulatory T cells establish an IL-10-IL10R immunometabolic checkpoint that limits HSL activation and lipolysis

Adipose tissue harbors a significant population of regulatory T (Treg) cells that enforce immune homeostasis, yet whether Tregs function as an immunometabolic checkpoint to directly regulate core adipocyte signaling programs remains incompletely defined. Here we show that adipose Tregs function as a dominant, time-dependent checkpoint on {beta}-adrenergic signal-driven lipolytic program and signal transduction in adipocytes. Our integrated scRNA-seq, flow cytometry, and phosphoproteomics data show that prolonged adrenergic stimulation induces a progressive attenuation of activation of key lipase hormone-sensitive lipase (HSL) that coincides with Treg depletion in circulation and accumulation within white adipose tissue. Genetic perturbations establish Treg-derived interleukin-10 (IL-10) as the key mediator of this brake. IL-10 signaling through adipocyte IL-10R suppresses adrenergic HSL activation and rewires downstream signaling nodes that govern catecholamine responsiveness, lipolysis, and systemic energy homeostasis. Mechanistically, IL-10R engages a STAT3-dependent transcriptional program that induces the G-protein regulators RGS2 and RGS3, diminished PKA flux to HSL that reinforces suppression of the HSL activation state and lipolysis. Together, these findings define an adrenergic-immune feedback circuit in which Tregs fine tune the amplitude and duration of catecholamine responsiveness in adipocytes, establishing immune control of a core lipolytic pathway with implications for obesity-associated adipose dysfunction.

cell biology↗

bioRxiv2026

Tetherin enforces an immunometabolic checkpoint that coordinates glycolytic and interferon signaling in adipocytes

Coordination between innate immune signaling and glucose metabolism is fundamental to organismal homeostasis, yet despite decades of study linking immunity and metabolism, the mechanisms by which metabolic cells restrain antiviral innate signaling while preserving glycolytic competence during overnutrition remain poorly defined. Here we identify Tetherin (BST2) as a unique cell-intrinsic immunometabolic checkpoint that couples restraint of type I interferon (IFN-I) signaling to preservation of glycolytic capacity in adipocytes. Tetherin localizes to endoplasmic reticulum and organizes an interactome enriched for antiviral sensing regulators and glycolytic control nodes in adipocytes. Mechanistically, Tetherin directly engages the ubiquitin-dependent degradation machinery NDFIP1 and RNF128 to terminate IRF3 activation, thereby limiting pro-inflammatory, anti-glycolytic signaling and protecting adipocytes from metabolic dysfunction. In parallel, multiomics integration reveals that Tetherin also acts as a scaffold that binds and spatially organizes and activates PFKFB3 to increase glycolytic capacity and restrain MAVS-IRF3 innate immune signalling. In vivo, adipocyte-specific loss of Tetherin amplifies high sucrose diet and high-fat-diet-induced glucose intolerance and liver steatosis, whereas overexpression of human Tetherin in adipocyte suppresses obesity-driven interferon signaling, restores glycolytic pathway, and improves metabolic homeostasis. Orthogonal perturbations in cancer and insulinoma cells further confirm an immunometabolic role for Tetherin. Together, these findings define Tetherin as a dual node immunometabolic checkpoint that couples restraint of antiviral innate inflammatory signaling to maintenance of glycolytic competence, thereby safeguarding adipocyte metabolic homeostasis.

cell biology↗

bioRxiv2026

Emergence of histone-based chromatin complexity in Asgard archaea

The emergence of the eukaryotes coincided with the diversification of histone proteins and their post-translational modifications by enzymes that constitute the core of eukaryotic chromatin. Yet the evolutionary origins of this regulatory machinery are unknown. Here, we show that the key molecular components of histone-based chromatin regulation are present in the Asgard archaea, the closest prokaryotic relatives of eukaryotes. Asgard histones are abundant and have extended N-terminal tails rich in lysine residues that can be post-translationally modified, all of which are features shared with eukaryotic histones. In line with these findings, we identify enzymes from Asgard archaea that deposit or remove lysine acetylation on histone tails in vitro. Moreover, Asgard sirtuin deacetylases (SIR2 proteins) restore chromatin silencing in yeast, demonstrating the functional compatibility of Asgard enzymes with eukaryotic histone substrates. Our findings establish that the foundations of histone-based chromatin predate eukaryogenesis and place Asgard archaea as an evolutionary intermediate in the emergence of eukaryotic chromatin.

evolutionary biology↗

bioRxiv2026

The genomic basis of evolutionary stasis in the 500-million-year-old red seaweed genus Ahnfeltia

The red seaweed genus Ahnfeltia is an ancient lineage that has persisted for over 500 million years with remarkably limited diversification despite a global distribution in cold-temperate intertidal habitats. Compared to the highly diverse sister lineage, Rhodymeniophycidae, Ahnfeltia provides a unique system for investigating long-term evolutionary persistence in marine macroalgae. Here, we generated chromosome-scale genomes from five populations across three species and combined population genomics with paleogeographic niche modelling. Our results reveal remarkable genomic conservation, strong geographic isolation with limited gene flow, high homozygosity, and evidence of purifying selection. Niche projections indicate long-term stability and spatial connectivity of suitable cold-temperate habitats. These findings suggest that Ahnfeltias persistence and limited diversification are linked to genomic constraints and stable ecological niches over geological timescales. This study provides new insights into the genomic basis of evolutionary stasis in ancient marine lineages and highlights potential vulnerability to ongoing climate change affecting cold-water coastal ecosystems.

evolutionary biology↗

bioRxiv2025

Major alleles of CDCA7α shape CG-methylation in Arabidopsis thaliana

DNA methylation is a key epigenetic mark that impacts gene expression and represses transposable elements (TEs) in eukaryotes. Numerous examples of cis-elements targeted by DNA methylation, particularly at CG sites (mCG), have been reported to be under selective pressure in animals and plants. By contrast, there is limited knowledge of trans-regulators of mCG leading to adaptation. Here, using genome-wide association studies, we identify CELL DIVISION CYCLE-ASSOCIATED PROTEIN 7 ALPHA (CDCA7) as a trans-regulator of mCG in natural populations of Arabidopsis thaliana. CDCA7 and its paralog, CDCA7{beta}, directly bind to the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1), which facilitates access of methyltransferases to DNA. CDCA7/{beta} selectively regulates mCG and minimally impacts other DDM1-dependent processes such as non-CG methylation and histone variant deposition. We identify the cis-regulatory sequence modulating CDCA7 expression in natural populations and determining the degree of mCG and TE silencing. The geographic distribution of CDCA7 alleles suggests that new alleles have repeatedly expanded to novel ecological niches, indicating a potential role in local adaptation. Altogether, our findings provide new insight into how changes in global DNA methylation levels through transcriptional regulation of the epigenetic machinery have the capacity to facilitate local adaptation.

plant biology↗

bioRxiv2025

High-Throughput Glycan Array Screening Reveals Rhamnogalacturonan-I as a Ligand for Arabidopsis Leucine-Rich Repeat Receptor Kinases

The plant cell wall not only serves as a physical barrier against pathogens but, when damaged, also functions as a source of cell wall-derived molecules that play crucial roles in plant immunity as damage-associated molecular patterns (DAMPs). While oligogalacturonides from homogalacturonan are well-studied DAMPs, the immune-signaling potential of other cell wall components remains largely unexplored. Conventional genetic and biochemical approaches aimed at identifying ligand-receptor pairs in plant immunity have been limited by the vast diversity of potential ligand molecules and functional redundancy of putative receptors. Here, we developed a high-throughput screening pipeline that simultaneously examines multiple interactions between plant cell wall-derived glycans and >350 extracellular domains (ECDs) of receptor kinases and receptor like proteins in Arabidopsis, resulting in the screening of >40,000 interactions. We discovered a group of leucine-rich repeat receptor kinases named ARMs (AWARENESS of RG-I MAINTENANCES) that interact with rhamnogalacturonan-I (RG-I), a major component of pectin. RG-I treatment induced pattern-triggered immunity responses, with distinct kinetics compared to oligogalacturonide responses. We identified RG-I oligosaccharide structures required for interaction with ARM receptors and immune activation, and found that ARM receptors are redundantly involved in plant immunity. Collectively, our approach provides a powerful platform for discovering glycan-receptor pairs in plants, facilitating a more comprehensive understanding of cell wall surveillance mechanisms in plant immunity.

plant biology↗

bioRxiv2024

Community-wide interactions sustain life in geothermal spring habitats

We investigated an alga-dominated geothermal spring community in Yellowstone National Park, USA. Our goal was to determine how cells cope with abiotic stressors during diurnal sampling that spanned over two orders of magnitude in solar irradiance. We report a community level response to toxic metal resistance and energy cycling that spans the three domains of life. Arsenic detoxification is accomplished via complementary gene expression by different lineages. Photosynthesis is dominated by Cyanidioschyzon, with the mixotroph, Galdieria, relegated to nighttime heterotrophy. Many key functions, including the cell cycle, are strongly regulated by diurnal light fluctuations. These results demonstrate that biotic interactions are highly structured in extreme habitats. We suggest this was also the case on the early Earth when geothermal springs were cradles of microbial life, prior to the origin of eukaryotes.

evolutionary biology↗

bioRxiv2024

SARM1 orthosteric base exchange inhibitors cause subinhibitory SARM1 activation

SARM1, an octameric NADase, is a key regulator of axon degeneration and an emerging target in small molecule drug discovery to treat a wide range of neurodegenerative diseases. Recently, a structurally diverse series of adduct-forming, orthosteric SARM1 inhibitors have been discovered. Here, we show that subinhibitory concentrations of these orthosteric inhibitors, under mildly SARM1 activating conditions, cause sustained SARM1 activation. This synergistic adverse effect leads to increased nicotinamide adenine dinucleotide (NAD) consumption, neurodegeneration and release of the biomarker neurofilament-light (NfL) in cultured cortical neurons. In two distinct animal models, we found that low-dose treatment with these orthosteric SARM1 inhibitors results in increased plasma NfL and adverse events when combined with cellular stress or injury conditions. This may present a critical liability for orthosteric SARM1 inhibitors in certain patient populations.

neuroscience↗

bioRxiv2023

Co-evolution of functional motifs and H2A.X in the context of DNA damage response identifies the plant Mediator of DNA Damage Checkpoint 1

Induction of DNA damage triggers rapid phosphorylation of the histone H2A.X ({gamma}H2A.X). In animals, mediator of DNA damage checkpoint 1 (MDC1) binds {gamma}H2A.X through a tandem BRCA1 carboxyl-terminal (tBRCT) domain and mediates recruitment of downstream effectors of DNA damage response (DDR). However, readers of this modification in plants have remained elusive. We report that from Arabidopsis BRCT domain proteome, BCP1-4 proteins with tBRCT domains are involved in DDR. Through its tBRCT domain BCP4 binds {gamma}H2A.X in vitro and localizes to DNA damage-induced foci in an H2A.X dependent manner. BCP4 also contains a domain that interacts directly with NBS1 and thus acts as a functional counterpart of MDC1. We also show that BCP1, that contains two tBRCT domains, co-localizes with {gamma}H2A.X but it does not bind {gamma}H2A.X suggesting functional similarity with human PAXIP1. A phylogenetic analysis supports that PAXIP1 and MDC1 in metazoa and their plant counterparts evolved independently from common ancestors with tBRCT domains. Collectively, our study reveals missing components and provides mechanistic and evolutionary insights into plant DDR.

cell biology↗

bioRxiv2019

Paulinella micropora KR01 holobiont genome assembly for studying primary plastid evolution

The widespread algal and plant (Archaeplastida) plastid originated >1 billion years ago, therefore relatively little can be learned about plastid integration during the initial stages of primary endosymbiosis by studying these highly derived species. Here we focused on a unique model for endosymbiosis research, the photosynthetic amoeba Paulinella micropora KR01 (Rhizaria) that underwent a more recent independent primary endosymbiosis about 124 Mya. A total of 149 Gbp of PacBio and 19 Gbp of Illumina data were used to generate the draft assembly that comprises 7,048 contigs with N50=143,028 bp and a total length of 707 Mbp. Genome GC-content was 44% with 76% repetitive sequences. We predicted 32,358 genes that contain 73% of the complete, conserved genes in the BUSCO database. The mean intron length was 882 bp, which is significantly greater than in other Rhizaria (86[~]184 bp). Symbiotic bacteria from the culture were isolated and completed genomes were generated from three species (Mesorhizobium amorphae Pch-S, Methylibium petroeiphilum Pch-M, Polaromonas sp. Pch-P) with one draft genome (Pimelobacter simplex Pch-N). Our holobiont data establish P. micropora KR01 as a model for studying plastid integration and the role of bacterial symbionts in Paulinella biology.

evolutionary biology↗

bioRxiv2018

The genome of Ectocarpus subulatus highlights unique mechanisms for stress tolerance in brown algae

Brown algae are multicellular photosynthetic stramenopiles that colonize marine rocky shores worldwide. Ectocarpus sp. Ec32 has been established as a genomic model for brown algae. Here we present the genome and metabolic network of the closely related species, Ectocarpus subulatus Kutzing, which is characterized by high abiotic stress tolerance. Since their separation, both strains show new traces of viral sequences and the activity of large retrotransposons, which may also be related to the expansion of a family of chlorophyll-binding proteins. Further features suspected to contribute to stress tolerance include an expanded family of heat shock proteins, the reduction of genes involved in the production of halogenated defence compounds, and the presence of fewer cell wall polysaccharide-modifying enzymes. Overall, E. subulatus has mainly lost members of gene families down-regulated in low salinities, and conserved those that were up-regulated in the same condition. However, 96% of genes that differed between the two examined Ectocarpus species, as well as all genes under positive selection, were found to encode proteins of unknown function. This underlines the uniqueness of brown algal stress tolerance mechanisms as well as the significance of establishing E. subulatus as a comparative model for future functional studies.

genomics↗