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

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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