Biology subjects

Shen, N.

Publications and source records attributed to Shen, N..

5 recordsLinked to original sources

bioRxiv2018

Genome-wide association study reveals sex-specific genetic architecture of facial attractiveness

Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 3,928 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci and highlighted a handful of candidate genes, many of which are specifically expressed in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.

genetics↗

bioRxiv2018

HDL-AuNPs-BMS nanoparticle conjugates as molecularly targeted therapy for leukemia

In previous work, gold nanoparticles (AuNPs) with adsorbed high-density lipoprotein (HDL) nanoparticles have been utilized to deliver oligonucleotides, yet HDL-AuNPs functionalized with small molecule inhibitors have not been systematically explored. Here, we report an AuNP-based therapeutic system (HDL-AuNPs-BMS) for acute myeloid leukemia (AML) by delivering BMS309403 (BMS), a small molecule that selectively inhibits AML-promoting factor fatty acid binding protein 4 (FABP4). HDL-AuNPs-BMS are synthesized using a gold nanoparticle as template to control conjugate size and ensure a spherical shape to engineer HDL-like nanoparticle containing BMS. The zeta potential and size of the HDL-AuNPs obtained from transmission electron microscopy (TEM) show that the nanoparticles are electrostatically stable and 25 nm in diameter. Functionally, compared to free drug, HDL-AuNPs-BMS conjugates are more readily internalized by AML cells and have more pronounced effect on downregulation of DNA methyltransferase 1 (DNMT1), reduction of global DNA methylation, and restoration of epigenetically-silenced tumor suppressor p15INK4b coupled with AML growth arrest. Importantly, systemic administration of HDL-AuNPs-BMS conjugates into AML-bearing mice inhibits DNMT1-dependent DNA methylation, induces AML cell differentiation and diminishes AML disease progression without obvious side effects. In summary, these data, for the first time, demonstrate HDL-AuNPs as an effective delivery platform with great potential to attach distinct inhibitors, and HDL-AuNPs-BMS conjugates as a promising therapeutic platform to treat leukemia.

cancer biology↗

bioRxiv2017

MicroRNA-21 Regulates Metabolic Adaptation of Pathogenic TH17 cells and Controls Autoimmune Inflammation

TH17 cells exhibit great heterogeneity and variable functional states in vivo. However, metabolic reprogramming of TH17 cells in vivo and its regulation during autoimmunity and host defence is unknown. Here we report that TH17 cells derived in vivo show discrete metabolic states. Metabolic states of TH17 cells in vivo were controlled at the epigenetic level, with conserved regulatory region of key metabolic regulators show distinct chromatin accessibility as demonstrated by chromatin landscape profiling. TGF-{beta}1 signaling was further shown to be crucial for remodeling of TH17 cell chromatin states, Ahr and miR-21 were identified as essential metabolic regulators for TH17 cells. Understanding metabolic reprogramming of TH17 cells in vivo may therefore provide more defined therapeutic intervention to TH17 cell mediated autoimmune diseases and insights into TH17 cell mediated host defence.

immunology↗

bioRxiv2017

Intrinsic specificity differences between transcription factor paralogs partly explain their differential in vivo binding

Members of transcription factor (TF) families, i.e. paralogous TFs, are oftentimes reported to have identical DNA-binding motifs, despite the fact that they perform distinct regulatory functions in the cell. Differential genomic targeting by paralogous TFs is generally assumed to be due to interactions with protein cofactors or the chromatin environment. Contrary to previous assumptions, we find that paralogous TFs have different intrinsic preferences for DNA, not captured by current motif models, and these differences partly explain differential genomic binding and functional specificity. Our finding was possible due to a unique combination of carefully designed high-throughput assays and rigorous computation modeling, integrated into a unified framework called iMADS. We used iMADS to quantify, model, and analyze specificity differences between 11 paralogous TFs from 4 distinct human TF families. Our finding of differential specificity between closely related TFs has important implications for the interpretation of the regulatory effects of non-coding genetic variants.

genomics↗

bioRxiv2017

T-bet+ CD11c+ B Cells Are Critical For Anti-Chromatin IgG Production In The Development Of Lupus

A hallmark of systemic lupus erythematosus is high titers of circulating autoantibody. A novel CD11c+ B cell subset has been identified that is critical for the development of autoimmunity. However, the role of CD11c+ B cells in the development of lupus is unclear. Chronic graft-versus-host disease (cGVHD) is a lupus-like syndrome with great autoantibody production. In the present study we investigated the role of CD11c+ B cells in the pathogenesis of lupus in the cGVHD model. Here, we found the percentage and absolute number of CD11c+ B cells and titer of sera anti-chromatin IgG and IgG2a antibody were increased in cGVHD mice. CD11c+ plasma cells from cGVHD mice produced large amounts of anti-chromatin IgG2a upon stimulation. Depletion of CD11c+ B cells reduced anti-chromatin IgG and IgG2a production. T-bet expression was further shown to be upregulated in CD11c+ B cells. Knockout of T-bet in B cells alleviated cGVHD. The percentage of T-bet+ CD11c+ B cells was elevated in lupus patients and positively correlated with serum anti-chromatin levels. Our findings suggest T-bet+ CD11c+ B cells contribute to the pathogenesis of lupus and provides potential target for therapeutic intervention.

immunology↗