Induction of Stem-Cell-Derived Functional Neurons by NanoScript-Based Gene Repression

被引:14
|
作者
Patel, Sahishnu [1 ]
Chueng, Sy-Tsong Dean [1 ]
Yin, Perry T. [2 ]
Dardir, Kholud [1 ]
Song, Zhichao [4 ]
Pasquale, Nicholas [1 ]
Kwan, Kelvin [4 ]
Sugiyama, Hiroshi [3 ]
Lee, Ki-Bum [1 ,2 ]
机构
[1] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA
[2] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA
[3] Kyoto Univ, Grad Sch Sci, Dept Chem, Kyoto 6068501, Japan
[4] Rutgers State Univ, Dept Cell Biol & Neurosci, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ 08854 USA
基金
美国国家科学基金会;
关键词
gene knockdown; NanoScript; nanoparticles; neuronal differentiation; transcription repressor proteins; TRANSCRIPTION FACTORS; GOLD NANOPARTICLES; SMALL MOLECULES; EXPRESSION; DIFFERENTIATION; PROTEINS; DELIVERY; BINDING; SIRNA; SOX9;
D O I
10.1002/anie.201504902
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Even though gene repression is a powerful approach to exogenously regulate cellular behavior, developing a platform to effectively repress targeted genes, especially for stem-cell applications, remains elusive. Herein, we introduce a nano-material-based platform that is capable of mimicking the function of transcription repressor proteins to downregulate gene expression at the transcriptional level for enhancing stem-cell differentiation. We developed the "NanoScript" platform by integrating multiple gene repression molecules with a nano-particle. First, we show a proof-of-concept demonstration using a GFP-specific NanoScript to knockdown GFP expression in neural stem cells (NSCs-GFP). Then, we show that a Sox9-specific NanoScript can repress Sox9 expression to initiate enhanced differentiation of NSCs into functional neurons. Overall, the tunable properties and gene-knockdown capabilities of NanoScript enables its utilization for generepression applications in stem cell biology.
引用
收藏
页码:11983 / 11988
页数:6
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