Genetic reprogramming of somatic cells into neuroblasts through a co-induction of the doublecortin gene along the Yamanaka factors: A promising approach to model neuroregenerative disorders

• Published in: Medical hypotheses 2019-06, Vol.127, p.105-111
• Main Authors: Kandasamy, Mahesh, Yesudhas, Ajisha, Poornimai Abirami, G.P., Radhakrishnan, Risna Kanjirassery, Roshan, Syed Aasish, Johnson, Esther, Ravichandran, Vijaya Roobini, Biswas, Abir, Shanmugaapriya, Sellathamby, Anusuyadevi, Muthuswamy, Aigner, Ludwig
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biomarkers; Cell Differentiation; Cellular Reprogramming; Doublecortin; Fibroblasts - cytology; Gene Expression Profiling; Genetic reprogramming; Humans; iPSCs; Microtubule-Associated Proteins - genetics; Models, Genetic; Neuroblasts; Neurodegenerative Diseases - diagnosis; Neurodegenerative Diseases - genetics; Neurodegenerative disorders; Neurons - cytology; Neuropeptides - genetics; Pluripotent Stem Cells - cytology; Stem Cell Transplantation
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2019.04.006

Neural stem cell (NSC) mediated adult neurogenesis represents the regenerative plasticity of the brain. The functionality of the neurogenic process appears to be operated by neuroblasts, the multipotent immature neuronal population of the adult brain. While neuroblasts have been realized to play a major role in synaptic remodeling and immunogenicity, neurodegenerative disorders have been characterized by failure in the terminal differentiation, maturation, integration and survival of newborn neuroblasts. Advancement in understanding the impaired neuroregenerative process along the neuropathological conditions has currently been limited by lack of an appropriate experimental model of neuroblasts. The genetic reprogramming of somatic cells into pluripotent state offers a potential strategy for the experimental modeling of brain disorders. Thus, the induced pluripotent stem cell (iPSC) based direct reprogramming of somatic cells into neuroblasts would represent a potential tool to understand the regenerative biology of the adult brain. Therefore, this concise article discusses the significance of iPSCs, the functional roles of neuroblasts in the adult brain and provides a research hypothesis for the direct reprogramming of somatic cells into neuroblasts through the co-induction of a potential proneurogenic marker, the doublecortin (DCX) gene along with the Yamanaka factors. The proposed cellular model of adult neurogenesis may provide us with further insights into neuropathogenesis of many neurodegenerative disorders and will provide a potential experimental platform for diagnostic, drug discovery and regenerative therapeutic strategies.