Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules

An-Dong Zhao; Hua Qin; Meng-Li Sun; Kui Ma; Xiao-Bing Fu

doi:10.1186/s40779-020-00271-7

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Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules

RESEARCH | Updated：2023-02-28

- Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules
- Military Medical Research Vol. 8, Issue 1, Pages: 62-78(2021)
- Affiliations：
  
  1.Tianjin Medical University, Tianjin 300070, China
  2.Research Center for Tissue Repair and Regeneration Affiliated to the Medical Innovation Research Division and 4th Medical Center, PLA General Hospital and PLA Medical College, 28 Fu Xing Road, Haidian District, Beijing 100853, China
  3.PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin Injury, Repair and Regeneration, Beijing 100048, China
  4.Research Unit of Trauma Care, Tissue Repair and Regeneration, Chinese Academy of Medical Sciences, Beijing 100048, China
- Author bio：
  
  * fuxiaobing@vip.sina.com
- Funds：
- DOI：10.1186/s40779-020-00271-7
  CLC：
- Published：2021-03
- Accepted：
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Zhao et al.: Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules. Mil Med Res, 2020, 7: 42.
DOI：

Zhao et al.: Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules. Mil Med Res, 2020, 7: 42. DOI： 10.1186/s40779-020-00271-7.

摘要

Abstract

Background:

Motor neuron degeneration or loss in the spinal cord is the characteristic phenotype of motor neuron diseases or spinal cord injuries. Being proliferative and located near neurons

astrocytes are considered ideal cell sources for regenerating neurons.

Methods:

We selected and tested different combinations of the small molecules for inducing the conversion of human and mouse astrocytes into neurons. Microscopic imaging and immunocytochemistry analyses were used to characterize the morphology and phenotype of the induced neurons while RT-qPCR was utilized to analyze changes in gene expression. In addition

whole-cell patch-clamp recordings were measured to examine the electrophysiological properties of induced neurons.

Results:

The results showed that human astrocytes could be rapidly and efficiently converted into motor neuronlike cells by treatment with defined small molecules

with a yield of over 85% motor neuron-like cells attained. The induced motor neuron-like cells expressed the pan-neuronal markers TUJ1

MAP2

NeuN

and Synapsin 1 and motor neuron markers HB9

ISL1

CHAT

and VAChT. During the conversion process

the cells did not pass through a proliferative neural progenitor cell intermediate. The induced motor neurons were functional

showing the electrophysiological properties of neurons. The same chemical cocktail could induce spinal cord astrocytes from an amyotrophic lateral sclerosis mouse model carrying a SOD1 mutation to become motor neuron-like cells that exhibited a decrease in cell survival and an increase in oxidative stress compared to that observed in wild-type MNs derived from healthy mice. Moreover

the chemical induction reduced oxidative stress in the mutant astrocytes.

Conclusions:

The results of the present study demonstrated the feasibility of chemically converting human and mouse astrocytes into motor neuron-like cells that are useful for neurodegenerative disease modeling and regenerative medicine.

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references

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