Reprogramming Astrocytes to Motor Neurons by Activation of Endogenous Ngn2 and Isl1

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2021 Jun 25

PMID 34171285

Citations 20

Authors

Meiling Zhou

Xiaoqing Tao

Ming Sui

Mengge Cui

Dan Liu

Beibei Wang

Ting Wang

Yunjie Zheng

Juan Luo

Yangling Mu

Feng Wan

Ling-Qiang Zhu

Bin Zhang

Affiliations

Soon will be listed here.

Abstract

Central nervous system injury and neurodegenerative diseases cause irreversible loss of neurons. Overexpression of exogenous specific transcription factors can reprogram somatic cells into functional neurons for regeneration and functional reconstruction. However, these practices are potentially problematic due to the integration of vectors into the host genome. Here, we showed that the activation of endogenous genes Ngn2 and Isl1 by CRISPRa enabled reprogramming of mouse spinal astrocytes and embryonic fibroblasts to motor neurons. These induced neurons showed motor neuronal morphology and exhibited electrophysiological activities. Furthermore, astrocytes in the spinal cord of the adult mouse can be converted into motor neurons by this approach with high efficiency. These results demonstrate that the activation of endogenous genes is sufficient to induce astrocytes into functional motor neurons in vitro and in vivo. This direct neuronal reprogramming approach may provide a novel potential therapeutic strategy for treating neurodegenerative diseases and spinal cord injury.

Citing Articles

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