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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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Zhang L,Yin JC,Yeh H,Ma NX,Lee G,Chen XA,Wang Y,Lin L,Chen L,Jin P,Wu GY,Chen G

doi

10.1016/j.stem.2015.09.012

subject

Has Abstract

pub_date

2015-12-03 00:00:00

pages

735-747

issue

6

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(15)00419-1

journal_volume

17

pub_type

杂志文章

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