Biology subjects

Lin, S.-R.

Publications and source records attributed to Lin, S.-R..

4 recordsLinked to original sources

bioRxiv2026

Public-Data Reanalysis Links MS4A4A to M2-like Human Myeloid States and Supports a Predicted Four-Pass Transmembrane Fold

Background/Objectives: MS4A4A is associated with M2-like macrophage states, while the MS4A gene cluster modifies soluble TREM2 levels and Alzheimer's disease risk. We asked whether MS4A4A consistently marks the M2 side of human myeloid activation and whether AlphaFold supports a proposed MS4A4A-MS4A6A interaction. Methods: We reanalysed four public human datasets: bulk RNA-seq and ATAC-seq of primary monocyte-derived macrophages from independent three-donor cohorts, and single-cell RNA-seq atlases of healthy liver and severe COVID-19 blood. MS4A4A and an MS4A4A-MS4A6A complex were modelled with AlphaFold 3 and evaluated using pLDDT, predicted aligned error, and ipTM. Results: MS4A4A was higher in M2 (IL-4) than in M1 (IFN-gamma; + LPS) macrophages in all three donors (log2 fold change +2.68, adjusted P = 0.0013). Its promoter showed the highest mean accessibility in M2. MS4A4A was macrophage-enriched in liver and monocyte-enriched in blood, and was detected in 76.7% of M2-like versus 39.3% of M1-like liver macrophages, with the difference driven mainly by the proportion of positive cells. AlphaFold confidently modelled the four transmembrane helices (mean pLDDT 83.1), but the predicted MS4A4A-MS4A6A interface was not supported (ipTM 0.59). Conclusions: MS4A4A is consistently associated with the M2 side of human myeloid activation across independent transcriptomic, chromatin, and single-cell datasets. The findings are associative, and the proposed MS4A4A-MS4A6A interface remains an untested structural hypothesis.

genomics↗

bioRxiv2024

Prophage-encoded Hm-oscar gene recapitulates Wolbachia-induced male killing in the tea tortrix moth Homona magnanima

Wolbachia are maternally transmitted bacterial symbionts that are ubiquitous among arthropods. They can hijack host reproduction in various ways, including male killing (MK), where the sons of infected mothers are killed during development. The recent discovery of MK-associated Wolbachia genes, i.e., oscar in Ostrinia moths and wmk in Drosophila flies, stimulates our interest in the diversity and commonality of MK mechanisms, which remain largely unclear. We recently discovered that a Wolbachia symbiont of the moth Homona magnanima carries an MK-associated prophage region encoding homologs of oscar (Hm-oscar) and wmk (wmk-1-4). Here, we investigated the effects of these genes in the native host. Upon transient overexpression, Hm-oscar, but not wmk, induced male lethality in H. magnanima, in contrast to our observations in Drosophila, where the wmk homologs, but not Hm-oscar, killed the males. Hm-oscar disrupted sex determination in male embryos by inducing a female-type doublesex splicing and impaired dosage compensation, recapitulating the Wolbachia phenotype. Cell-based transfection assays confirmed that Hm-oscar suppressed the function of masculinizer, the primary male sex determinant involved in lepidopteran dosage compensation. Our study highlights the conserved roles of oscar homologs in Wolbachia-induced lepidopteran MK and argues that Wolbachia have evolved multiple MK mechanisms in insects.

evolutionary biology↗

bioRxiv2023

MiR-221/222-enriched ADSC-exosome mitigates PM exposure-exacerbated cardiac ischemia/reperfusion injury through the modulation of the BNIP3/LC3B/PUMA pathway

BackgroundEpidemiology has demonstrated a strong relationship between fine particulate matter (PM) exposure and cardiovascular disease. Whether PM aggravates myocardial ischemia/reperfusion (I/R) injury and its related mechanisms remain unclear. Our previous study showed that adipose stem cell-derived exosomes (ADSC-Exo) contain a large amount of miR-221/222. This study investigated the effects of PM exposure on I/R-induced cardiac injury through mitophagy and apoptosis, as well as the potential role of miR-221/222 in ADSC-Exo. MethodsWild-type, miR-221/222 knockout (miR-221/222 KO), and miR-221/222 overexpressed transgenic (miR-221/222 TG) mice were intratracheally injected with 100 g/kg PM for 24 h before I/R treatment. Ischemia was induced by temporarily occluding the left anterior descending (LAD) coronary artery with sutures for 30 min, followed by 3 h of reperfusion. In an in vitro model, H9c2 cells were exposed to 50 g/mL PM for 6 h and subjected to hypoxia (1% O2) at 37{degrees}C for 6 h, followed by 12 h reoxygenation. ResultsPM aggravates I/R (H/R)-induced cardiac injury by increasing ROS levels and causing mitochondrial dysfunction, leading to an increase in mitochondrial fission-related proteins like Drp1 and Mff, mitophagy-related proteins such as BNIP3 and LC3B, as well as apoptosis-related proteins like PUMA and p-p53 in vivo and in vitro studies. In comparison, transfection of ADSC-Exo and miR-221/222 mimics significantly reduced PM+I/R (H/R)-induced cardiac injury. Importantly, ADSC-Exo contains miR-221/222, which directly targets BNIP3, LC3B, and PUMA, decreasing their expression and ultimately reducing cardiomyocyte mitophagy and apoptosis. ConclusionsThe study showed that PM aggravates I/R or H/R-induced cardiac injury, and ADSC-Exo treatment significantly reduced this by regulating mitophagy and apoptosis through miR-221/222/BNIP3/LC3B/PUMA.

cell biology↗

bioRxiv2022

Male-killing-associated bacteriophage WO identified from comparisons of Wolbachia endosymbionts of Homona magnanima

The origin and mechanism of male-killing, an advantageous strategy employed by maternally transmitted symbionts such as Wolbachia, remain unclear. We compared genomes of four Wolbachia strains derived from Homona magnanima, a male-killing strain wHm-t (1.5 Mb), and three non-male-killing strains, wHm-a (1.1 Mb), wHm-b (1.3 Mb), and wHm-c (1.4 Mb). A wHm-t-specific 76-kbp prophage region harboured two tandemly arrayed WO-mediated killing (wmk) gene homologs (wmk-1/wmk-2 and wmk-3/wmk-4). Of these, wmk-1 or wmk-3 killed almost all Drosophila melanogaster individuals when transgenically overexpressed. Dual expression of wmk-3 and wmk-4 killed all males and rescued females. We propose a novel hypothesis wherein horizontally transmitted proto-Wolbachia with a single wmk killed both sexes, and tandem duplication of wmk allowed an evolutionary transition to a vertically transmitted symbiont, causing male-killing. Our study highlights the bacteriophage as a critical driver of the evolution of male-killing and argues for a conserved male-killing mechanism in diverse insects.

evolutionary biology↗