@article{6cea5161f2de4391986bb2715a2e527d,
title = "Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons",
abstract = "We have recently demonstrated that reactive glial cells can be directly reprogrammed into functional neurons by a single neural transcription factor, NeuroD1. Here we report that a combination of small molecules can also reprogram human astrocytes in culture into fully functional neurons. We demonstrate that sequential exposure of human astrocytes to a cocktail of nine small molecules that inhibit glial but activate neuronal signaling pathways can successfully reprogram astrocytes into neurons in 8-10 days. This chemical reprogramming is mediated through epigenetic regulation and involves transcriptional activation of NEUROD1 and NEUROGENIN2. The human astrocyte-converted neurons can survive for >5 months in culture and form functional synaptic networks with synchronous burst activities. The chemically reprogrammed human neurons can also survive for >1 month in the mouse brain in vivo and integrate into local circuits. Our study opens a new avenue using chemical compounds to reprogram reactive glial cells into functional neurons.",
author = "Lei Zhang and Yin, {Jiu Chao} and Hana Yeh and Ma, {Ning Xin} and Grace Lee and Chen, {Xiangyun Amy} and Yanming Wang and Li Lin and Li Chen and Peng Jin and Wu, {Gang Yi} and Gong Chen",
note = "Funding Information: We would like to thank Yuting Bai and Yi Hu for technical support and the Chen laboratory members for vigorous discussion and helpful comments during the progress of this project. This work was supported by grants from National Institutes of Health (MH083911 and AG045656) and Pennsylvania State University Stem Cell Fund to G.C. and the Recruitment Program of High-end Foreign Experts of the State Administration of Foreign Experts Affairs (GDT20144400031) to G.-Y.W. Funding Information: We would like to thank Yuting Bai and Yi Hu for technical support and the Chen laboratory members for vigorous discussion and helpful comments during the progress of this project. This work was supported by grants from National Institutes of Health (MH083911 and AG045656) and Pennsylvania State University Stem Cell Fund to G.C. and the Recruitment Program of High-end Foreign Experts of the State Administration of Foreign Experts Affairs (GDT20144400031) to G.-Y.W. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = dec,
day = "3",
doi = "10.1016/j.stem.2015.09.012",
language = "English (US)",
volume = "17",
pages = "735--747",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "6",
}