Induction of human neuronal cells by defined transcription factors

Induction of human neuronal cells by defined transcription factors

2012 February 11 | Zhiping P. Pang, Nan Yang, Thomas Vierbuchen, Austin Ostermeier, Daniel R. Fuentes, Troy Q. Yang, Ami Citri, Vittorio Sebastiano, Samuele Marro, Thomas C. Südhof, and Marius Wernig
The study demonstrates that a combination of three transcription factors—Brn2 (Pou3f2), Ascl1, and Myt1—can efficiently convert human pluripotent stem cells into functional neurons within 6 days of transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors can also convert fetal and postnatal human fibroblasts into neurons with typical neuronal morphologies and markers. The majority of these induced neurons (iN cells) generate action potentials and form synapses when co-cultured with primary mouse cortical neurons. This method provides a robust approach for generating patient-specific human neurons for disease modeling and regenerative medicine applications.The study demonstrates that a combination of three transcription factors—Brn2 (Pou3f2), Ascl1, and Myt1—can efficiently convert human pluripotent stem cells into functional neurons within 6 days of transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors can also convert fetal and postnatal human fibroblasts into neurons with typical neuronal morphologies and markers. The majority of these induced neurons (iN cells) generate action potentials and form synapses when co-cultured with primary mouse cortical neurons. This method provides a robust approach for generating patient-specific human neurons for disease modeling and regenerative medicine applications.
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