4.5 Article

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

Journal

MEDICAL HYPOTHESES
Volume 127, Issue -, Pages 105-111

Publisher

ELSEVIER
DOI: 10.1016/j.mehy.2019.04.006

Keywords

iPSCs; Doublecortin; Neuroblasts; Genetic reprogramming; Neurodegenerative disorders

Funding

  1. Faculty Recharge Programme, University Grants Commission (UGC-FRP), New Delhi, India
  2. DST-SERB, New Delhi, India [DST-SERB EEQ/2016/000639, DST-SERB ECR/2016/000741]
  3. DST-SERB [EEQ/2016/000639, ECR/2016/000741]
  4. Department of Biotechnology (DBT), New Delhi, India [DBT/2018/BDU/1112]
  5. FWF Special Research Program (SFB) F44 Cell Signaling in Chronic CNS Disorders [F4413-B23]
  6. BMWFW D-CogPlast Project [BMWFW-10.420/0009-WF/V/3c/2015]
  7. FWF project [P31362-B34]

Ask authors/readers for more resources

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.

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