Induction of Stem Cell-derived Functional Neurons via NanoScript-based Gene Repression

Details

• Alternative Title:
  Angew Chem Int Ed Engl
• Personal Author:
  Patel, Sahishnu ; Chueng, Sy-Tsong Dean ; Yin, Perry T. ; Dardir, Kholud ; Song, Zhichao ; Pasquale, Nicholas ; Kwan, Kelvin ; Sugiyama, Hiroshi ; Lee, Ki-Bum
• Description:
  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 nanomaterial-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 nanoparticle. 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 gene-repression applications in stem cell biology.
• Keywords:
  Biomimetic Materials Biomimetics Gene Expression Gene Knockdown Gene Knockdown Techniques Gene Regulation Green Fluorescent Proteins Humans Nanoparticles Neural Stem Cells Neurogenesis Neuronal Differentiation Neurons Nylons Promoter Regions, Genetic Repressor Proteins SOX9 Transcription Factor Transcription Repressor Proteins

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• Source:
  Angew Chem Int Ed Engl. 54(41):11983-11988
• Pubmed ID:
  26292201
• Pubmed Central ID:
  PMC5568028
• Document Type:
  Journal Article
• Funding:
  R01 DC015000/DC/NIDCD NIH HHSUnited States/ ; R21 NS085569/NS/NINDS NIH HHSUnited States/ ; 1DP20D006462-01/DP/NCCDPHP CDC HHSUnited States/ ; 1R21NS085569-01/NS/NINDS NIH HHSUnited States/
• Volume:
  54
• Issue:
  41
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:84d16e599938c5ba3bf653e217d7a7eb06f01441c0700f2f330b70b5b2645881
• Download URL:
  https://stacks.cdc.gov/view/cdc/47731/cdc_47731_DS1.pdf
• File Type:
  [PDF - 938.45 KB ]