ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Sonic Hedgehog Effectively Improves Oct4-Mediated Reprogramming of Astrocytes into Neural Stem Cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- PBAE nanoparticle-mediated delivery of ASCL1 and NGN2 genes for astroglia-to-neuron reprogramming to remodel glial scar for spinal cord injury repair.Stem cell research & therapy · 2026Article
- Research progress on the Sonic Hedgehog signaling pathway in the central nervous system: Novel insights.Neural regeneration research · 2026Article
- The Small Chemical Compound Repsox Potentiates Oct4-Driven Astrocyte-to-Neural Stem Cell Reprogramming via Notch1/Hes1/Smurf2 Pathway.Cellular and molecular neurobiology · 2026Article
- Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.Molecular cancer · 2026Article
- A dual role for GLI3 signaling in neural crest development.Development (Cambridge, England) · 2026Article
- Ptbp1 knockdown induces conversion of rat spinal cord astrocytes into neuron like cells.Scientific reports · 2025Article
- Development of a Lentiviral Reporter System for In Vitro Reprogramming of Astrocytes to Neuronal Precursors.Biology · 2025Article
- Emerging roles of ribosome translation in stem cells and stem cell therapy - a review.Cell & bioscience · 2025Review
- OCT4 protein and gene expression analysis in the differentiation of spermatogonia stem cells into neurons by immunohistochemistry, immunocytochemistry, and bioinformatics analysis.Stem cell reviews and reports · 2023Article
- Regulation of Morphogenetic Processes during Postnatal Development and Physiological Regeneration of the Adrenal Medulla.Bulletin of experimental biology and medicine · 2023Article
- Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion.Cell death & disease · 2023Article
- Generation of neural organoids for spinal-cord regeneration via the direct reprogramming of human astrocytes.Nature biomedical engineering · 2023Article
- Modification of Müller Glial Cell Fate and Proliferation with the Use of Small Molecules.Advances in experimental medicine and biology · 2023Review
- Rho Kinase Inhibitor Y27632 Improves Recovery After Spinal Cord Injury by Shifting Astrocyte Phenotype and Morphology via the ROCK/NF-κB/C3 Pathway.Neurochemical research · 2022Article
- Generation of a Pure Culture of Neuron-like Cells with a Glutamatergic Phenotype from Mouse Astrocytes.Biomedicines · 2022Article
- RhoA/ROCK signaling pathway and astrocytes in ischemic stroke.Metabolic brain disease · 2021Review
- Review
- Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy.Frontiers in cellular neuroscience · 2021Review
- 1-[(4-Nitrophenyl)sulfonyl]-4-phenylpiperazine treatment after brain irradiation preserves cognitive function in mice.Neuro-oncology · 2020Article
- Adult neurogenesis from reprogrammed astrocytes.Neural regeneration research · 2020Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Irreversible neuron loss following spinal cord injury (SCI) usually results in persistent neurological dysfunction. The generation of autologous neural stem cells (NSCs) holds great potential for neural replenishment therapies and drug screening in SCI. Our recent studies demonstrated that mature astrocytes from the spinal cord can directly revert back to a pluripotent state under appropriate signals. However, in previous attempts, the reprogramming of astrocytes into induced NSCs (iNSCs) was unstable, inefficient, and frequently accompanied by generation of intermediate precursors. It remained unknown how to further increase the efficiency of astrocyte reprogramming into iNSCs. Here, we show that mature astrocytes could be directly converted into iNSCs by a single transcription factor, Oct4, and that the iNSCs displayed typical neurosphere morphology, authentic NSC gene expression, self-renewal capacity, and multipotency. Strikingly, Oct4-driven reprogramming of astrocytes into iNSCs was potentiated with continuous sonic hedgehog (Shh) stimulation, as demonstrated by a sped-up reprogramming and increased conversion efficiency. Moreover, the iNSC-derived neurons possessed functionality as neurons. Importantly, crosstalk between Sox2/Shh-targeted downstream signals and phosphatidylinositol 3-kinase/cyclin-dependent kinase 2/Smad ubiquitin regulatory factor 2 (PI3K/Cdk2/Smurf2) signaling is likely involved in the mechanisms underlying this cellular event. The highly efficient reprogramming of astrocytes to generate iNSCs will provide an alternative therapeutic approach for SCI using autologous cells.
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