1. Academic Validation
  2. Chemical conversion of human and mouse fibroblasts into motor neurons

Chemical conversion of human and mouse fibroblasts into motor neurons

  • Sci China Life Sci. 2018 Oct;61(10):1151-1167. doi: 10.1007/s11427-018-9359-8.
Hua Qin 1 2 Andong Zhao 1 2 Kui Ma 2 Xiaobing Fu 3 4
Affiliations

Affiliations

  • 1 Graduate School of Tianjin Medical University, Tianjin, 300070, China.
  • 2 Cell Biology and Tissue Repair Laboratory, Key Laboratory of Wound Repair and Regeneration of PLA, First Affiliated Hospital of PLA General Hospital, Beijing, 100048, China.
  • 3 Cell Biology and Tissue Repair Laboratory, Key Laboratory of Wound Repair and Regeneration of PLA, First Affiliated Hospital of PLA General Hospital, Beijing, 100048, China. fuxiaobing@vip.sina.com.
  • 4 College of Life Sciences, PLA General Hospital, PLA Medical College, Beijing, 100853, China. fuxiaobing@vip.sina.com.
Abstract

Transplantation of motor neurons can provide long-term functional benefits in animal models of neurodegenerative motor neuron diseases such as amyotrophic lateral sclerosis and traumatic spinal cord injury. Although embryonic stem cells can differentiate into motor neurons, alternative sources of motor neurons may be controllable for disease modeling and transplantation. Here, we show that human and mouse fibroblasts can be efficiently and directly converted into motor neurons by a cocktail of five small molecules, without the involvement of the neural progenitor stage. The chemically-induced motor neurons display the distinct neuronal morphology and express motor neuron markers. Interestingly, when the same chemical compounds were soaked in beads and implanted in the hypodermis of the back skins of mice, surrounding cells begin to express motor neuron markers, indicating in vivo motor neuron reprogramming. Taken together, we provide an efficient approach for chemically converting human and mouse fibroblasts into motor neurons suitable for cell replacement therapy and neurodegenerative disease modeling.

Keywords

conversion; fibroblast; motor neuron; neurodegenerative diseases; regeneration; reprogramming; small molecule; transdifferentiation.

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