The iNs and Outs of Direct Reprogramming to Induced Neurons.
| Autor: | Carter JL; Gene Therapy Center, Stem Cell Program, Department of Neurology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA, United States., Halmai JANM; Gene Therapy Center, Stem Cell Program, Department of Neurology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA, United States., Fink KD; Gene Therapy Center, Stem Cell Program, Department of Neurology, Institute for Regenerative Cures, University of California, Davis, Sacramento, CA, United States. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in genome editing [Front Genome Ed] 2020 Sep 04; Vol. 2, pp. 7. Date of Electronic Publication: 2020 Sep 04 (Print Publication: 2020). |
| DOI: | 10.3389/fgeed.2020.00007 |
| Abstrakt: | Understanding of cell-type specific transcription factors has promoted progress in methods for cellular reprogramming, such as directly reprogramming somatic cells to induced neurons (iN). Methods for direct reprogramming require neuronal-fate determining gene activation via neuron-specific microRNAs, chemical modulation of key neuronal signaling pathways or overexpression via viral vectors, with some reprogramming strategies requiring a combination of these methods to induce the neuronal-cell fate. These methods have been employed in a multitude of cell types, including fibroblasts, hepatocytes, peripheral blood mononuclear, and T cells. The ability to create iN from skin biopsies and blood samples coupled with recent advancements in artificially inducing age- and disease-associated phenotypes are accelerating the development of disease models for late-onset neurodegenerative disorders. Here, we review how activation of the neuronal transcriptome alters the epigenetic landscape of the donor cell to facilitate reprogramming to neurons. We also discuss the advantages of using DNA binding domains such as CRISPR/dCas9 to overcome epigenetic barriers to induce neuronal-cell fate by activating endogenous neuronal cell-fate determining genes. (Copyright © 2020 Carter, Halmai and Fink.) |
| Databáze: | MEDLINE |
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