Browsing by Author "Sun, Ning"

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    Engineering human ventricular heart muscles based on a highly efficient system for purification of human pluripotent stem cell-derived ventricular cardiomyocytes
    (BMC, 2017-09-29) Li, Bin; Yang, Hui; Wang, Xiaochen; Zhan, Yongkun; Sheng, Wei; Cai, Huanhuan; Xin, Haoyang; Liang, Qianqian; Zhou, Ping; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yang, Pengyuan; Zhang, Jianyi; Shou, Weinian; Huang, Guoying; Liang, Ping; Sun, Ning; Pediatrics, School of Medicine
    Background Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish. Methods The purification system used TALEN-mediated genomic editing techniques to insert the neomycin or EGFP selection marker directly after the myosin light chain 2 (MYL2) locus in human pluripotent stem cells. Purified early ventricular cardiomyocytes were estimated by immunofluorescence, fluorescence-activated cell sorting, quantitative PCR, microelectrode array, and patch clamp. In subsequent experiments, the mixture of mature MYL2-positive ventricular cardiomyocytes and mesenchymal cells were cocultured with decellularized natural heart matrix. Histological and electrophysiology analyses of the formed tissues were performed 2 weeks later. Results Human ventricular cardiomyocytes were efficiently isolated based on the purification system using G418 or flow cytometry selection. When combined with the decellularized natural heart matrix as the scaffold, functional human ventricular heart muscles were prepared in a dish. Conclusions These engineered human ventricular muscles can be great tools for regenerative therapy of human ventricular damage as well as drug screening and ventricular-specific disease modeling in the future. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0651-x) contains supplementary material, which is available to authorized users.
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    Enhanced Ionic Accessibility of Flexible MXene Electrodes Produced by Natural Sedimentation
    (Springer, 2020-04-11) Sun, Ning; Guan, Zhaoruxin; Zhu, Qizhen; Anasori, Babak; Gogotsi, Yury; Xu, Bin; Mechanical and Energy Engineering, School of Engineering and Technology
    MXene nanosheets have been used for preparing highly flexible integrated electrodes due to their two-dimensional (2D) morphology, flexibility, high conductivity, and abundant functional groups. However, restacking of 2D nanosheets inhibits the ion transport in MXene electrodes, limiting their thickness, rate performance, and energy storage capacity. Here, we employed a natural sedimentation method instead of the conventional vacuum-assisted filtration to prepare flexible Ti3C2Tx MXene films with enlarged interlayer spacing, which facilitates the access of the lithium ions to the interlayers and thus leads to a greatly enhanced electrochemical performance. The naturally sedimented flexible film shows a double lithium storage capacity compared to the conventional vacuum-filtered MXene film, along with improved rate performance and excellent cycle stability.
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    QKI is a critical pre-mRNA alternative splicing regulator of cardiac myofibrillogenesis and contractile function
    (Springer Nature, 2021-01-04) Chen, Xinyun; Liu, Ying; Xu, Chen; Ba, Lina; Liu, Zhuo; Li, Xiuya; Huang, Jie; Simpson, Ed; Gao, Hongyu; Cao, Dayan; Sheng, Wei; Qi, Hanping; Ji, Hongrui; Sanderson, Maria; Cai, Chen-Leng; Li, Xiaohui; Yang, Lei; Na, Jie; Yamamura, Kenichi; Liu, Yunlong; Huang, Guoying; Shou, Weinian; Sun, Ning; Pediatrics, School of Medicine
    The RNA-binding protein QKI belongs to the hnRNP K-homology domain protein family, a well-known regulator of pre-mRNA alternative splicing and is associated with several neurodevelopmental disorders. Qki is found highly expressed in developing and adult hearts. By employing the human embryonic stem cell (hESC) to cardiomyocyte differentiation system and generating QKI-deficient hESCs (hESCs-QKIdel) using CRISPR/Cas9 gene editing technology, we analyze the physiological role of QKI in cardiomyocyte differentiation, maturation, and contractile function. hESCs-QKIdel largely maintain normal pluripotency and normal differentiation potential for the generation of early cardiogenic progenitors, but they fail to transition into functional cardiomyocytes. In this work, by using a series of transcriptomic, cell and biochemical analyses, and the Qki-deficient mouse model, we demonstrate that QKI is indispensable to cardiac sarcomerogenesis and cardiac function through its regulation of alternative splicing in genes involved in Z-disc formation and contractile physiology, suggesting that QKI is associated with the pathogenesis of certain forms of cardiomyopathies.