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Transdifferentiate Astrocytes to Neurons by Knockdown of Polypyrimidine Tract Binding Protein 1 for Treatment of Spinal Cord Injury

Author(s): Yunyi Zhu, Changling Yue, Qianwen Yang, Zhaohuan Zhang and Xiaohui Xu*
School of Life Sciences, Shanghai University, Shanghai 200444, 1Department of Laboratory Medicine, Changzheng Hospital, Naval Medical University, Shanghai 200003, 2School of Preclinical Medicine, Wannan Medical College, Wuhu, Anhui 241002, China

Correspondence Address:
Xiaohui Xu, School of Preclinical Medicine, Wannan Medical College, Wuhu, Anhui 241002, China, E-mail:

This study investigated the feasibility of polypyrimidine tract binding protein 1 knockout mouse spinal cord astrocytes in the treatment of spinal cord injury. We cultured primary astrocytes from the spinal cord of newborn mice, then integrated sh polypyrimidine tract binding protein 1 into the genome by lentiviral transduction and verified their knockout efficiency. Immunofluorescence staining and transcriptome sequencing were performed to test whether the cells differentiated into neurons. The results showed that polypyrimidine tract binding protein 1 knockout could transform spinal cord astrocytes into functional neurons in one step. After whole transcriptome sequencing analysis, gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enriched differentially expressed genes revealed that mitogen-activated protein kinase, erythroblastic oncogene B and Ras-associated protein-1 signaling pathways may be involved in this transdifferentiating process. Predictive analysis of microRNA target genes revealed microRNAs that may be involved in neural differentiation, as well as long noncoding RNA and circular RNA that indirectly regulate transdifferentiating through these microRNAs. Analysis of the circular RNA-microRNA-messenger RNA network revealed three circular RNA that may play a key role in transdifferentiating, as well as possible regulatory mechanisms in this process. We further constructed a mouse spinal cord injury model and found that 9 w after surgery, the basso mouse scale score of the right hind limb of the sh polypyrimidine tract binding protein 1 lentivirus injection group was significantly higher than that of the scrambled lentivirus injection group. Our results suggest that polypyrimidine tract binding protein 1 knockdown of reactively proliferating spinal cord astrocytes in spinal cord injury promotes neuron generation.

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