Biology subjects

Ge, G.

Publications and source records attributed to Ge, G..

5 recordsLinked to original sources

bioRxiv2026

ZDHHC14-Mediated Palmitoylation of TBK1 Promotes Pathological Cardiac Hypertrophy via Type I Interferon Signaling Activation

Pathological cardiac hypertrophy represents a common maladaptive response to cardiovascular stress and constitutes a major harbinger of heart failure. Although S-palmitoylation--a reversible post-translational modification--critically governs protein localization, trafficking, and stability, its involvement in cardiac hypertrophy remains poorly characterized. In this study, we aimed to explore the role and regulatory mechanism of a palmitoyltransferase, zinc finger DHHC-type palmitoyltransferase 14 (ZDHHC14), in cardiac hypertrophy. We found that ZDHHC14 was significantly upregulated in cardiac hypertrophy tissues from both human patients and mouse models. Cardiomyocyte-specific ZDHHC14 knockdown ameliorated transverse aortic constriction (TAC)-induced cardiac hypertrophy and dysfunction in male mice, whereas cardiac-specific ZDHHC14 overexpression via AAV9 exacerbated these pathological phenotypes. Mechanistically, TANK-binding kinase 1 (TBK1) was identified as a novel substrate of ZDHHC14 through interactomic screening. ZDHHC14 catalyzed TBK1 palmitoylation at cysteine 267, which in turn facilitated TBK1 phosphorylation and subsequent activation of type I interferon (IFN-I) signaling, ultimately promoting cardiac hypertrophy. Importantly, our findings demonstrate that the TBK1-C267S mutation rectifies ZDHHC14 overexpression-induced exacerbation of cardiac hypertrophy. This study illustrated a ZDHHC14-TBK1-IFN-I axis in regulating cardiac hypertrophy, which may provide a potential therapeutic target to ameliorate pathological cardiac hypertrophy.

molecular biology↗

bioRxiv2026

Ryder: Epigenome normalization using a two-tier model and internal reference regions

Motivation: Sequencing-based epigenomic profiling methods are powerful but suffer from technical variability that complicates cross-sample comparisons and can obscure true biological signals. While existing normalization methods using spike-in controls or computational approaches have been proposed, they often rely on assumptions that may not hold across diverse experimental conditions or require additional data types. Results: We present Ryder, a flexible and robust Python package for the normalization of epigenomic signal tracks. Ryder leverages stable internal reference regions, such as invariant CTCF binding sites, to correct for technical artifacts genome-wide. Our results show that it effectively adjusts both background noise and signal intensity, ensuring accurate signal alignment across samples while preserving genuine biological differences. We demonstrate that Ryder performs robustly across diverse assays including DNase-seq, CUT&RUN, ATAC-seq, MNase-seq, and ChIP-seq, with or without spike-in controls. By reducing technical noise, Ryder improves the detection of genuine biological changes, such as quantitative reduction of chromatin accessibility at key enhancer elements by depletion of BRG1, a key subunit of the chromatin remodeling BAF complexes. Availability and Implementation: The Ryder source code, documentation and test data are freely available at: https://github.com/YaqiangCao/ryder . The software version used in this study is archived at Zenodo: https://zenodo.org/records/21267457 .

bioinformatics↗

bioRxiv2023

GLI1 facilitates rheumatoid arthritis by collaborative regulation of DNA methyltransferases

Rheumatoid arthritis (RA) is characterized by joint synovitis and bone destruction, the etiology of which remains to be explored. Overactivation of M1 macrophages and osteoclasts has been thought a direct cause of joint inflammation and bone destruction. Glioma-associated oncogene homolog 1 (GLI1) has been revealed to be closely linked to bone metabolism. In this study, GLI1-expression in synovial tissue of RA patients showed to be positively correlated with RA-related scores and was highly expressed in collagen-induced arthritis (CIA) mouse articular macrophage-like cells. The decreased expression and inhibition of nuclear transfer of GLI1 downregulated macrophage M1 polarization and osteoclast activation, the effect of which was achieved by modulation of DNA methyltransferases (DNMTs) via transcriptional regulation and protein interaction ways. By pharmacological inhibition of GLI1, the proportion of proinflammatory macrophages and the number of osteoclasts were significantly reduced, and the joint inflammatory response and bone destruction in CIA mice were alleviated. This study clarified the mechanism of GLI1 in macrophage phenotypic changes and activation of osteoclasts, suggesting potential applications of GLI1 inhibitor in the clinical treatment of RA.

cell biology↗

bioRxiv2019

Protein adlayer thickness on colloidal nanoparticle determined by Rayleigh-Gans-Debye approximation

Reference materials (RM)-assisted Rayleigh-Gans-Debye approximation (rm-RGDA) has been developed and used to in situ determine the size and thickness of the adlayer on the particles in solution. The particle size determined by rm-RGDA is quite close to that measured by electron microscopy but significantly smaller than that measured by DLS. The BSA adlayer absorbed on PS50, PS100 and SiO2 NPs is 3.3, 0.9 and 1.2 nm, respectively, and close to those observed by SEM, which is 4.6, 1.3 and 3.8 nm, respectively. The FTIR analysis results show that the BSA absorbed on larger particles or hydroxyl-abundant surface, e.g. PS100 and SiO2 NPs can lose its secondary structure, e.g. -helix, to a great extent and that absorbed on a more curve surface, e.g. smaller PS50 particles can largely preserve its secondary structure as its free state. The measurement results show the curvature of the NPs is closely related to the structure change of the adsorbed protein. This method provide a facile and new approach to measure the size and its adlayer change of the hybrid and core-shell structured nanoparticles in a wide range of wavelength. SIGNIFICANCEQuantitative study on the adsorption of the protein on colloidal nanoparticles is an important approach to understand the biophysical effect, compared with other ex situ methods such as TEM and SEM, where the specimen are undergone pre-processing and no longer the original state in measurement. It is, therefore, a big challenge. In order to cope with this challenge, UV-vis based RGDA has been developed and applied to in situ measure the size of the dispersed colloidal nanoparticles and their protein adlayer thickness, where the protein adlayer thickness on the colloidal nanoparticles can be easily determined. We believe this method provide a facile and sensitive way to in situ measure the dimension change of hybrid colloidal nanoparticles.

biophysics↗

bioRxiv2018

TCF7L2 Regulation of GATA6-dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia

Genetic variations in Wnt-coreceptor LRP6 and Wnt-regulated transcription factor TCF7L2 have been among the strongest genetic signals for type2 diabetes (T2DM) and coronary artery disease (CAD). Mice with a CAD-linked LRP6 mutation exhibit obstructive coronary artery disease characterized by reduced TCF7L2 expression and dedifferentiation of vascular smooth muscle cell (VSMC). While TCF7L2 maintains stemness and promotes proliferation in embryonic tissues and adult stem cells, its role and mechanisms of action in VSMC differentiation is not understood. Using multiple mouse models, we demonstrate here that TCF7L2 promotes differentiation and inhibits proliferation of VSMCs. TCF7L2 accomplishes these effects by stabilization of GATA6 and upregulation of SM-MHC and cell cycle inhibitors. Accordingly, TCF7L2 haploinsufficient mice exhibited increased susceptibility to, while mice overexpressing TCF7L2 were protected against injury-induced intimal hyperplasia compared to wildtype littermates. Consequently, the overexpression of TCF7L2 in LRP6 mutant mice rescued the injury induced intimal hyperplasia. These novel findings imply cell type-specific functional role of TCF7L2 and provide critical insight into poorly understood mechanisms underlying pathogenesis of intimal hyperplasia.

molecular biology↗