Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons

Lei Zhang, Jiu Chao Yin, Hana Yeh, Ning Xin Ma, Grace Lee, Xiangyun Amy Chen, Yanming Wang, Li Lin, Li Chen, Peng Jin, Gang Yi Wu, Gong Chen

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)735-747
Number of pages13
JournalCell Stem Cell
Volume17
Issue number6
DOIs
StatePublished - Dec 3 2015

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Cell Biology

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