Biology subjects

Geng, Z.

Publications and source records attributed to Geng, Z..

25 records · Page 2Linked to original sources

bioRxiv2022

The transcription factor RXRA regulates lipid metabolism in duck myoblasts by the CD36 network

Lipid metabolism is a highly complex metabolic process regulated at multiple levels. RXRA is a well-characterized factor that regulates lipid metabolism. To explore the function and mechanism of the transcription factor RXRA in myoblasts, and to further explore the key factors that RXRA regulates the target gene CD36 signaling network to regulate lipid metabolism. We found that the transcription factor RXRA inhibited the accumulation of triglycerides (TGs), cholesterol (CHOL) and non-esterified fatty acids (NEFA) in CS2 cells by regulating CD36 as well as the fatty acid beta oxidation pathway. CD36 functions similar to RXRA in myoblasts. CD36 overexpression reduced the levels of TGs, CHOL, NEFAs and saturated fatty acids (SFAs) in these cells, while CD36 knockout increased the levels of TGs, CHOL, NEFAs, SFAs and monounsaturated fatty acids (MUPAs) in these cells. GRB2, MAP1B, SLC38A1, SLC4A7, NCOA3, PKIA, MOB2, SAA2 and RXRA are involved in the CD36 promotion of lipid efflux through lipid metabolism, endocytosis and amino acid metabolism. Considering these results, we propose that RXRA regulates lipid metabolism in myoblasts by regulating the CD36 signaling network.

molecular biology↗

bioRxiv2021

A Recurring Chemogenetic Switch for Chimeric Antigen Receptor T Cells

As a revolutionary cancer treatment, the chimeric antigen receptor (CAR) T cell therapy suffers from complications such as cytokine release syndromes and T cell exhaustion. Their mitigation desires controllable activation of CAR-T cells that is achievable through regulatory display of CARs on the T cell surface. By embedding the hepatitis C virus NS3 protease (HCV-NS3) in an anti-CD19 CAR between the anti-CD19 single-chain variable fragment (scFv) and the hinge domain, we showed that the display of anti-CD19 scFv on CAR-T cells was positively correlated to the presence of a clinical HCV-NS3 inhibitor asunaprevir (ASV). This novel CAR design that allows the display of anti- CD19 scFv on the T cell surface in the presence of ASV and its removal in the absence of ASV effectuates a practically recurring chemical switch for CAR-T cells. We demonstrated that the intact CAR on T cells was repeatedly turn on and off by controlling the presence of ASV. The dose dependent manner of the intact CAR display on T cells with regard to the ASV concentration enables delicate modulation of CAR-T cell activation during cancer treatment. In a mouse model, we showed different treatment prospects when ASV was provided at different doses to mice that were infused with both human CD19+ lymphoma and the switchable CAR-T cells.

bioengineering↗

bioRxiv2021

AUTS2 controls neuronal lineage choice through a novel PRC1-independent complex and BMP inhibition

Despite a prominent risk factor for Neurodevelopmental disorders (NDD), it remains unclear how Autism Susceptibility Candidate 2 (AUTS2) controls the neurodevelopmental program. Our studies investigated the role of AUTS2 in neuronal differentiation and discovered that AUTS2, together with WDR68 and SKI, forms a novel protein complex (AWS) specifically in neuronal progenitors and promotes neuronal differentiation through inhibiting BMP signaling. Genomic and biochemical analyses demonstrated that the AWS complex achieves this effect by recruiting the CUL4 E3 ubiquitin ligase complex to mediate poly-ubiquitination and subsequent proteasomal degradation of phosphorylated SMAD1/5/9. Furthermore, using primary cortical neurons, we observed aberrant BMP signaling and dysregulated expression of neuronal genes upon manipulating the AWS complex, indicating that the AWS-CUL4-BMP axis plays a role in regulating neuronal lineage specification in vivo. Thus, our findings uncover a sophisticated cellular signaling network mobilized by a prominent NDD risk factor, presenting multiple potential therapeutic targets for NDD.

biochemistry↗

bioRxiv2020

Biochar effect - mediated ammonium transporter genes and GDH may be the core of improvement nitrogen assimilation in cotton seedling

Biochar enhancement of nitrogen efficiency in crops is highly essential not only to reduce costs of agricultural production but also to conserve resources, lower energy consumption for products of these fertilizers, strengthen soil health, and eventually helps in slowing climate change; however nitrogen efficiency physiology by biochar effects is not clear. Here, we reported on the morphological, nitrogen metabolism and cytokinin, at seedling stage, under different layers of biochar and limited urea conditions grown in soil culture. Expression profile of miRNAs and AOB was further studied in fine and medium roots. It showed active root absorption area, fresh weight, and nitrogen agronomic efficiency responded significantly under biochar and reduction by 20% urea condition in the surface soil layer. Also, NR and GPT activity in fine roots remarkably increased with cytokinin, but decreased significantly in medium roots, meanwhile both NR and GDH activity did so. GOGAT activity was to be dependent with biochar and urea locations. In addition, AMT1;1, gdh3 and gdh2 in fine roots showed their up-regulation with reduction 20% urea and biochar. It revealed that co-expression of gdh3 and gdh2 in fine roots significantly affected nitrogen assimilation under reduction 20% urea with biochar on surface soil at seedling stage. HighlightsThe co-expression of ammonium transporter gene and GDH induced by biochar effect improves nitrogen efficiency and seedling growth. These data emphasizes the importance of effects of cytokinin on nitrate reductase activity closely related to the position under biochar condition, which is a key element of enhancement nitrogen assimilation efficiency in cotton seedling. Biochar addition applied into 0 to 10cm soil had a more positive effect on seedling growth than that into 10 to 20cm soil layers.

plant biology↗

bioRxiv2019

Satellite Imaging of Global Urbanicity relate to Adolescent Brain Development and Behavior

Urbanicity, the impact of living in urban areas, is among the greatest environmental challenges for mental health. While urbanicity might be distinct in different sociocultural conditions and geographic locations, there are likely to exist common features shared in different areas of the globe. Understanding these common and specific relations of urbanicity with human brain and behavior will enable to assess the impact of urbanicity on mental disorders, especially in childhood and adolescence, where prevention and early interventions are likely to be most effective.\n\nWe constructed from satellite-based remote sensing data a factor for urbanicity that was highly correlated with population density ground data. This factor, UrbanSat was utilized in the Chinese CHIMGEN sample (N=831) and the longitudinal European IMAGEN cohort (N=810) to investigate if exposure to urbanicity during childhood and adolescence is associated with differences in brain structure and function in young adults, and if these changes are linked to behavior.\n\nUrbanicity was found negatively correlated with medial prefrontal cortex volume and positively correlated with cerebellar vermis volume in young adults from both China and Europe. We found an increased correlation of urbanicity with functional network connectivity within- and between- brain networks in Chinese compared to European participants. Urbanicity was highly correlated with a measure of perceiving a situation from the perspective of others, as well as symptoms of depression in both datasets. These correlations were mediated by the structural and functional brain changes observed. Susceptibility to urbanicity was greatest in two developmental windows during mid-childhood and adolescence.\n\nUsing innovative technology, we were able to probe the relationship between urban upbringing with brain change and behavior in different sociocultural conditions and geographic locations. Our findings help to identify shared and distinct determinants of adolescent brain development and mental health in different regions of the world, thus contributing to targeted prevention and early-intervention programs for young people in their unique environment. Our approach may be relevant for public health, policy and urban planning globally.

neuroscience↗

bioRxiv2019

Mutant p53 Drives Clonal Hematopoiesis through Modulating Epigenetic Pathway

Clonal hematopoiesis of indeterminate potential (CHIP) increases with age and is associated with increased risks of hematological malignancies. While TP53 mutations have been identified in CHIP, the molecular mechanisms by which mutant p53 promotes hematopoietic stem and progenitor cell (HSPC) expansion are largely unknown. We discovered that mutant p53 confers a competitive advantage to HSPCs following transplantation and promotes HSPC expansion after radiation-induced stress. Mechanistically, mutant p53 interacts with EZH2 and enhances its association with the chromatin, thereby increasing the levels of H3K27me3 in genes regulating HSPC self-renewal and differentiation. Further, genetic and pharmacological inhibition of EZH2 decrease the repopulating potential of p53 mutant HSPCs. Thus, we have uncovered an epigenetic mechanism by which mutant p53 drives clonal hematopoiesis. Our work will likely establish epigenetic regulator EZH2 as a novel therapeutic target for preventing CHIP progression and treating hematological malignancies with TP53 mutations.

cancer biology↗

bioRxiv2018

Hypothalamic transcriptome analysis reveals the neuroendocrine mechanisms in controlling broodiness of Muscovy duck (Cairina moschata)

Broodiness, one of the maternal behaviors and instincts for natural breeding in birds, is an interesting topic in reproductive biology. Broodiness in poultry is characterized by persistent nesting, usually associated with cessation of egg laying. The study of avian broodiness is essential for bird conservation breeding and commercial poultry industry. In this study, we examined the hypothalamus transcriptome of Muscovy duck in three reproductive stages, including egg-laying anaphase (LA), brooding prophase (BP) and brooding metaphase (BM). Differences in gene expression during the transition from egg-laying to broodiness were examined, and 155, 379, 292 differently expressed genes (DEGs) were obtained by pairwise comparisons of LA-vs-BP, LA-vs-BM and BP-vs-BM, respectively (fold change[≥] 1.5, P < 0.05). Gene Ontology Term (GO) enrichment analysis suggested a possible role of oxidative stress in the hypothalamus might invoke reproductive costs that potentially change genes expression. KEGG analysis revealed glutamatergic synapse, dopaminergic synapse, serotonergic synapse and GABAergic synapse pathway were significantly enriched, and regulator genes were identified. Eight gene expression patterns were illustrated by trend analysis and further clustered into three clusters. Additional six hub genes were identified through combining trend analysis and protein-protein interaction (PPI) analysis. Our results suggested that the cyclical mechanisms of reproductive function conversion include effects of oxidative stress, biosynthesis of neurotransmitters or their receptors, and interactions between glucocorticoids and thyroid hormones and regulatory genes. These candidate genes and biological pathways may be used as targets for artificial manipulation and marker-assisted breeding in the reproductive behavior.

animal behavior and cognition↗