MicroRNA-Mediated In Vitro and In Vivo Direct Conversion of Astrocytes to Neuroblasts

The conversion of astrocytes to neuroblasts holds great promise for treatment of neurodegenerative and traumatic brain diseases. Here we have shown that adult human astrocytes could be reprogrammed to neuroblasts by miR-302/367, both in vivo and in vitro. However, the reprogramming of adult mouse as...

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Bibliographic Details
Published in:PloS one 2015-06, Vol.10 (6), p.e0127878-e0127878
Main Authors: Ghasemi-Kasman, Maryam, Hajikaram, Maryam, Baharvand, Hossein, Javan, Mohammad
Format: Article
Language:English
Subjects:
Animals
Astrocytes
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - metabolism
Brain
Brain research
Cell Differentiation - drug effects
Cells, Cultured
Developmental biology
Direct conversion
Epigenetics
Fibroblasts
Gene expression
Histone deacetylase
Humans
Laboratory animals
Male
Medical research
Medical treatment
Mice
Mice, Inbred C57BL
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Neural Stem Cells - cytology
Neural Stem Cells - metabolism
Neuroblasts
Neuroglia - cytology
Neuroglia - metabolism
Neurological diseases
Neuronal-glial interactions
Neurons
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
Patch-Clamp Techniques
Physiology
Pluripotency
Ribonucleic acid
RNA
Science
Stem cells
Transcription factors
Traumatic brain injury
Valproic acid
Valproic Acid - pharmacology
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Summary:The conversion of astrocytes to neuroblasts holds great promise for treatment of neurodegenerative and traumatic brain diseases. Here we have shown that adult human astrocytes could be reprogrammed to neuroblasts by miR-302/367, both in vivo and in vitro. However, the reprogramming of adult mouse astrocytes to neuroblasts required valproic acid (VPA), a histone deacetylase inhibitor. Following induction of astrocytes toward neurons the expression of pluripotency markers were not detected, which suggested direct cell conversion. We did not observed tumor formation during two months follow up. These results show that neuroblasts can be generated directly from adult human and mouse astrocytes by miR-302/367-driven induction. This approach seems promising for converting glial scar cells into neuroblasts in a wide range of neurological diseases.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0127878