ArticleFrontiers in bioengineering and biotechnology2018
Transdifferentiating Astrocytes Into Neurons Using ASCL1 Functionalized With a Novel Intracellular Protein Delivery Technology.
Article in Frontiers in bioengineering and biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- A promise for neuronal repair: reprogramming astrocytes into neurons in vivo.Bioscience reports · 2024Review
- MicroRNA Roles in Cell Reprogramming Mechanisms.Cells · 2022Review
- Direct Reprogramming of Somatic Cells to Neurons: Pros and Cons of Chemical Approach.Neurochemical research · 2021Article
- Induced Neurons for Disease Modeling and Repair: A Focus on Non-fibroblastic Cell Sources in Direct Reprogramming.Frontiers in bioengineering and biotechnology · 2021Review
- Neuronal Reprogramming for Tissue Repair and Neuroregeneration.International journal of molecular sciences · 2020Review
- Combination of Chemical and Neurotrophin Stimulation Modulates Neurotransmitter Receptor Expression and Activity in Transdifferentiating Human Adipose Stromal Cells.Stem cell reviews and reports · 2019Article
- Next-generation disease modeling with direct conversion: a new path to old neurons.FEBS letters · 2019Review
- Lipo-PEG-PEI complex as an intracellular transporter for protein therapeutics.International journal of nanomedicine · 2019Article
- Reprogramming astrocytes into dopaminergic neurons to restore motor dysfunction in ParkinsonZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciencesArticle
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular transdifferentiation changes mature cells from one phenotype into another by altering their gene expression patterns. Manipulating expression of transcription factors, proteins that bind to DNA promoter regions, regulates the levels of key developmental genes. Viral delivery of transcription factors can efficiently reprogram somatic cells, but this method possesses undesirable side effects, including mutations leading to oncogenesis. Using protein transduction domains (PTDs) fused to transcription factors to deliver exogenous transcription factors serves as an alternative strategy that avoids the issues associated with DNA integration into the host genome. However, lysosomal degradation and inefficient nuclear localization pose significant barriers when performing PTD-mediated reprogramming. Here, we investigate a novel PTD by placing a secretion signal sequence next to a cleavage inhibition sequence at the end of the target transcription factor-achaete scute homolog 1 (ASCL1), a powerful regulator of neurogenesis, resulting in superior stability and nuclear localization. A fusion protein consisting of the amino acid sequence of ASCL1 transcription factor with this novel PTD added can transdifferentiate cerebral cortex astrocytes into neurons. Additionally, we show that the synergistic action of certain small molecules improves the efficiency of the transdifferentiation process. This study serves as the first step toward developing a clinically relevant
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Registered trials
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