How to reprogram human fibroblasts to neurons

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.

Molecular Components of Store-Operated Calcium Channels in the Regulation of Neural Stem Cell Physiology, Neurogenesis, and the Pathology of Huntington’s Disease

“…Various protocols to obtain MSNs from iPSCs have been developed ( Zhang et al, 2010 ; Delli Carri et al, 2013 ; Arber et al, 2015 ; Lin et al, 2015 ; Liu et al, 2016 ; Nekrasov et al, 2016 ; Adil et al, 2018 ; Golas, 2018 ; Csobonyeiova et al, 2020 ; Grigor’eva et al, 2020 ; Xu et al, 2020 ; Vigont et al, 2021 ). These protocols may be based on other already established protocols that are modified.…”

“…Forskolin is a cAMP signal conduction activator and not widely used for MSN terminal differentiation. However, it is a morphogen that is used for the direct differentiation of fibroblasts into cholinergic and glutaminergic neurons and motoneurons ( Xu et al, 2020 ). Dibutyryl-cAMP (db-cAMP) is a cAMP analog that is used more frequently ( Zhang et al, 2010 ; Nicoleau et al, 2013 ; Victor et al, 2014 ; Lin et al, 2015 ; Adil et al, 2018 ; Grigor’eva et al, 2020 ).…”

Cellular Models in Schizophrenia Research

“…NPCs are first formed during the iPSC-to-neuron transition. NPCs may also be derived from neural stem cells (NSCs) isolated from the olfactory epithelium (OE) or through direct reprogramming (trans-differentiation) of non-neural cells [39]. NPCs form a homogeneous population after a few passages and continue to proliferate in the presence of fibroblast growth factor 2 as adherent monolayers.…”

Optimization of Neurite Tracing and Further Characterization of Human Monocyte-Derived-Neuronal-like Cells

“…Not surprisingly, published manuscripts involving IPSCs and neurodevelopmental disorders comprise rather small cohorts. Another emerging methodology consists of directly reprogramming somatic cells, often fibroblasts, directly into neurons [ 25 , 26 ]. This approach, known as induced neurons (iNs), bypasses the need for dedifferentiation but still requires altering the cell’s genome [ 25 , 26 ].…”

“…Another emerging methodology consists of directly reprogramming somatic cells, often fibroblasts, directly into neurons [ 25 , 26 ]. This approach, known as induced neurons (iNs), bypasses the need for dedifferentiation but still requires altering the cell’s genome [ 25 , 26 ]. The potential confounding effects of reprograming and the need to show reproducible results when studying neurodevelopmental disorders remain.…”