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Publication : Reprogramming astrocytes to motor neurons by activation of endogenous Ngn2 and Isl1.

First Author  Zhou M Year  2021
Journal  Stem Cell Reports Volume  16
Issue  7 Pages  1777-1791
PubMed ID  34171285 Mgi Jnum  J:350018
Mgi Id  MGI:6727657 Doi  10.1016/j.stemcr.2021.05.020
Citation  Zhou M, et al. (2021) Reprogramming astrocytes to motor neurons by activation of endogenous Ngn2 and Isl1. Stem Cell Reports 16(7):1777-1791
abstractText  Central nervous system injury and neurodegenerative diseases cause irreversible loss of neurons. Overexpression of exogenous specific transcription factors can reprogram somatic cells into functional neurons for regeneration and functional reconstruction. However, these practices are potentially problematic due to the integration of vectors into the host genome. Here, we showed that the activation of endogenous genes Ngn2 and Isl1 by CRISPRa enabled reprogramming of mouse spinal astrocytes and embryonic fibroblasts to motor neurons. These induced neurons showed motor neuronal morphology and exhibited electrophysiological activities. Furthermore, astrocytes in the spinal cord of the adult mouse can be converted into motor neurons by this approach with high efficiency. These results demonstrate that the activation of endogenous genes is sufficient to induce astrocytes into functional motor neurons in vitro and in vivo. This direct neuronal reprogramming approach may provide a novel potential therapeutic strategy for treating neurodegenerative diseases and spinal cord injury.
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