MicroRNA-mediated conversion of human fibroblasts to neurons

MicroRNA-mediated conversion of human fibroblasts to neurons

2012 May 09 | Andrew S. Yoo, Alfred X. Sun, Li Li, Aleksandr Shcheglovitov, Thomas Portmann, Yulong Li, Chris Lee-Messer, Ricardo E. Dolmetsch, Richard W. Tsien, and Gerald R. Crabtree
This study investigates the role of microRNAs (miRNAs) in neuronal differentiation, focusing on miR-9* and miR-124. The authors found that these miRNAs induce human fibroblasts to differentiate into neurons, a process facilitated by the neurogenic transcription factor *NEUROD2*. The addition of other neurogenic transcription factors, such as *ASCL1* and *MYT1*, further enhances the conversion rate and maturation of the converted neurons. The study demonstrates that the genetic circuitry involving miR-9/9* and miR-124 plays an instructive role in neural fate determination. The induced neurons exhibit typical neuronal characteristics, including action potentials, voltage-gated ion currents, and synaptic activity. The conversion process is also effective in adult human dermal fibroblasts, although more slowly. This work highlights the potential of using miRNAs and neurogenic transcription factors to induce various types of neurons.This study investigates the role of microRNAs (miRNAs) in neuronal differentiation, focusing on miR-9* and miR-124. The authors found that these miRNAs induce human fibroblasts to differentiate into neurons, a process facilitated by the neurogenic transcription factor *NEUROD2*. The addition of other neurogenic transcription factors, such as *ASCL1* and *MYT1*, further enhances the conversion rate and maturation of the converted neurons. The study demonstrates that the genetic circuitry involving miR-9/9* and miR-124 plays an instructive role in neural fate determination. The induced neurons exhibit typical neuronal characteristics, including action potentials, voltage-gated ion currents, and synaptic activity. The conversion process is also effective in adult human dermal fibroblasts, although more slowly. This work highlights the potential of using miRNAs and neurogenic transcription factors to induce various types of neurons.
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[slides and audio] MicroRNA-mediated conversion of human fibroblasts to neurons