Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2015 Oct 21

PMID 26481520

Citations 143

Authors

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

Affiliations

Soon will be listed here.

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.

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