How to reprogram human fibroblasts to neurons

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How to reprogram human fibroblasts to neurons Ziran Xu1, Shengnan Su2, Siyan Zhou3, Wentao Yang4, Xin Deng4, Yingying Sun1,3, Lisha Li1*  and Yulin Li1*

Abstract  Destruction and death of neurons can lead to neurodegenerative diseases. One possible way to treat neurodegenerative diseases and damage of the nervous system is replacing damaged and dead neurons by cell transplantation. If new neurons can replace the lost neurons, patients may be able to regain the lost functions of memory, motor, and so on. Therefore, acquiring neurons conveniently and efficiently is vital to treat neurological diseases. In recent years, studies on reprogramming human fibroblasts into neurons have emerged one after another, and this paper summarizes all these studies. Scientists find small molecules and transcription factors playing a crucial role in reprogramming and inducing neuron production. At the same time, both the physiological microenvironment in vivo and the physical and chemical factors in vitro play an essential role in the induction of neurons. Therefore, this paper summarized and analyzed these relevant factors. In addition, due to the unique advantages of physical factors in the process of reprogramming human fibroblasts into neurons, such as safe and minimally invasive, it has a more promising application prospect. Therefore, this paper also summarizes some successful physical mechanisms of utilizing fibroblasts to acquire neurons, which will provide new ideas for somatic cell reprogramming. Keywords:  Human fibroblasts, Reprogramming, Transcriptional factors, Small molecules, Physical factors, Neurons Introduction Three major steps happen in the human body during the development of CNS (central nervous system): the neurogenesis and mitosis of neural progenitor cells, migration to a particular position and differentiation of neurons under gene regulation [1]. Neural progenitor cells will be able to differentiate into neurons and neuroglial cells during human’s whole life cycle [2]. Neuroglial cells differentiated from neural progenitor cells provide microenvironment for the proliferation and growth of neurons, participating in neuronal signaling and immune defense [3–6]. Neurons can be divided into sensory neurons, motor neurons, and interneurons based on different functions [7–9]. Another way of classification shows *Correspondence: [email protected]; [email protected] 1 The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130021, People’s Republic of China Full list of author information is available at the end of the article

that neuronal surface receptors are different, so the neurotransmitter signals they receive are different. Therefore, people can treat neurological diseases by aiming at different surface receptors of neurons. For example, the antagonist against the ­ GABAA receptor can improve spatial learning in rats, which is hoped to treat Alzheimer’s disease [10]. In addition, there are experiments usin