RETRACTED ARTICLE: Senescence impairs direct conversion of human somatic cells to neurons

Chong-kui Sun, Di Zhou, Zhen Zhang, Liming He, Fan Zhang, Xiaowei Wang, Jie Yuan, Qianming Chen, Ling-Gang Wu () and Qin Yang ()
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Chong-kui Sun: Washington University School of Medicine
Di Zhou: Washington University School of Medicine
Zhen Zhang: National Institute of Neurological Disorders and Stroke
Liming He: National Institute of Neurological Disorders and Stroke
Fan Zhang: Washington University School of Medicine
Xiaowei Wang: Washington University School of Medicine
Jie Yuan: Medical College, Jinan University
Qianming Chen: State Key Laboratory of Oral Diseases, Sichuan University
Ling-Gang Wu: National Institute of Neurological Disorders and Stroke
Qin Yang: Washington University School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Recent reports have shown that fibroblasts can be converted to neurons by forced expression of transcription factors. However, the mechanisms underlying this conversion remain unclear. Here, we show that the efficiency of neuronal conversion of embryonic human fibroblasts aged in culture is lower than that in cells in early culture stages. Moreover, depletion of p16Ink4a and p19Arf involved in the activation of cellular senescence is sufficient to convert human fibroblast and epithelial cells into neurons. The induced neurons express neuron-specific proteins, generate action potentials and neurotransmitter receptor-mediated currents. Genome-wide transcriptional analysis shows that the induced neurons have a profile different from fibroblasts and similar to that of control neurons induced by established methods. We further noted that expression of p53 blocks the neuronal conversion, whereas expression of human telomerase reverse transcriptase (hTERT) induces it. Our results indicate that overcoming senescence is a crucial step for neuronal conversion of somatic cells.

Date: 2014
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DOI: 10.1038/ncomms5112

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