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, Qin Yang

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 p16 Ink4a 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.

Original languageEnglish
Article number4112
JournalNature communications
Volume5
DOIs
StatePublished - Jun 17 2014

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