Directing neuronal cell fate in vitro: Achievements and challenges

Abstract

Human pluripotent stem cell (PSC) technology and direct somatic cell reprogramming have opened up a promising new avenue in the field of neuroscience. These recent advances allow researchers to obtain virtually any cell type found in the human brain, making it possible to produce and study functional neurons in laboratory conditions for both scientific and medical purposes. Although distinct approaches have shown to be successful in directing neuronal cell fate in vitro, their refinement and optimization, as well as the search for alternative approaches, remains necessary to help realize the full potential of the eventually derived neuronal populations. Furthermore, we are currently limited in the number of neuronal subtypes whose induction is fully established, and different cultivation protocols for each subtype exist, making it challenging to increase the reproducibility and decrease the variances that are observed between different protocols. In this review, we summarize the progress that has been made in generating various neuronal subtypes from PSCs and somatic cells, with special emphasis on chemically defined systems, transcription factor-mediated reprogramming and epigenetic-based approaches. We also discuss the efforts that are being made to increase the efficiency of current protocols and address the potential for the use of these cells in disease modelling, drug discovery and regenerative medicine.

3D Bioprinting Pluripotent Stem Cell Derived Neural Tissues Using a Novel Fibrin Bioink Containing Drug Releasing Microspheres

“…One of the challenges when working with hiPSCs is ensuring their differentiation into the desired, mature phenotypes. Neural differentiation of hiPSCs can take months and require a significant amount of labor and resources (Riemens et al, 2018). One promising strategy for promoting such differentiation requires treating these hiPSCs with small molecule morphogens (Zhang et al, 2012).…”

Dynamin‐related protein 1: A critical protein in the pathogenesis of neural system dysfunctions and neurodegenerative diseases

“…Mitochondria, the “power house” of the cell for producing the ATP, always change their morphology in terms of number and size through fusion and fission events‐called mitochondrial dynamics (Burte, Carelli, Chinnery, & Yu‐Wai‐Man, ; Eisner, Picard, & Hajnoczky, ; Liesa, Palacin, & Zorzano, ; Nasrallah & Horvath, ; Wai & Langer, ). Neurons are a special type of cell with a very high demand for energy, and they have unique axonal and dendritic structures that are responsible for the transmission of various signals in the brain and control many physiological activities of human body (Fricker, Tolkovsky, Borutaite, Coleman, & Brown, ; Riemens, van den Hove, Esteller, & Delgado‐Morales, ; Yamada, Adachi, Fukaya, Iijima, & Sesaki, ; Zeng & Sanes, ).…”

Direct reprogramming of fibroblasts into diverse lineage cells by DNA demethylation followed by differentiating cultures

“…An achievement of neuronal cell fate and identity by direct lineage reprogramming was a research subject of most attention in the field of regenerative medicine in company with cardiomyocyte due to clinical significance [ 11 , 30 ]. A majority of studies to produce functional neurons have been undertaken by transcription factor-mediated cellular reprogramming along the lines of iPSC production [ 30 ].…”