Browsing by Author "Zhang, Meng"

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    T Cell Repertoire Diversity Is Decreased in Type 1 Diabetes Patients
    (Elsevier, 2016) Tong, Yin; Li, Zhoufang; Zhang, Hua; Xia, Ligang; Zhang, Meng; Xu, Ying; Wang, Zhanhui; Deem, Michael W.; Sun, Xiaojuan; He, Jiankui
    Type 1 diabetes mellitus (T1D) is an immune-mediated disease. The autoreactive T cells in T1D patients attack and destroy their own pancreatic cells. In order to systematically investigate the potential autoreactive T cell receptors (TCRs), we used a high-throughput immune repertoire sequencing technique to profile the spectrum of TCRs in individual T1D patients and controls. We sequenced the T cell repertoire of nine T1D patients, four type 2 diabetes (T2D) patients, and six nondiabetic controls. The diversity of the T cell repertoire in T1D patients was significantly decreased in comparison with T2D patients (P = 7.0E−08 for CD4+ T cells, P = 1.4E−04 for CD8+ T cells) and nondiabetic controls (P = 2.7E−09 for CD4+ T cells, P = 7.6E−06 for CD8+ T cells). Moreover, T1D patients had significantly more highly-expanded T cell clones than T2D patients (P = 5.2E−06 for CD4+ T cells, P = 1.9E−07 for CD8+ T cells) and nondiabetic controls (P = 1.7E−07 for CD4+ T cells, P = 3.3E−03 for CD8+ T cells). Furthermore, we identified a group of highly-expanded T cell receptor clones that are shared by more than two T1D patients. Although further validation in larger cohorts is needed, our data suggest that T cell receptor diversity measurements may become a valuable tool in investigating diabetes, such as using the diversity as an index to distinguish different types of diabetes.
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    The sound of silence: Transgene silencing in mammalian cell engineering
    (Cell Press, 2022) Cabrera, Alan; Edelstein, Hailey I.; Glykofrydis, Fokion; Love, Kasey S.; Palacios, Sebastian; Tycko, Josh; Zhang, Meng; Lensch, Sarah; Shields, Cara E.; Livingston, Mark; Weiss, Ron; Zhao, Huimin; Haynes, Karmella A.; Morsut, Leonardo; Chen, Yvonne Y.; Khalil, Ahmad S.; Wong, Wilson W.; Collins, James J.; Rosser, Susan J.; Polizzi, Karen; Elowitz, Michael B.; Fussenegger, Martin; Hilton, Isaac B.; Leonard, Joshua N.; Bintu, Lacramioara; Galloway, Kate E.; Deans, Tara L.
    To elucidate principles operating in native biological systems and to develop novel biotechnologies, synthetic biology aims to build and integrate synthetic gene circuits within native transcriptional networks. The utility of synthetic gene circuits for cell engineering relies on the ability to control the expression of all constituent transgene components. Transgene silencing, defined as the loss of expression over time, persists as an obstacle for engineering primary cells and stem cells with transgenic cargos. In this review, we highlight the challenge that transgene silencing poses to the robust engineering of mammalian cells, outline potential molecular mechanisms of silencing, and present approaches for preventing transgene silencing. We conclude with a perspective identifying future research directions for improving the performance of synthetic gene circuits.