Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2022; 14(6): 393-419
Published online Jun 26, 2022. doi: 10.4252/wjsc.v14.i6.393
Application and prospects of high-throughput screening for in vitro neurogenesis
Shu-Yuan Zhang, Juan Zhao, Jun-Jun Ni, Hui Li, Zhen-Zhen Quan, Hong Qing
Shu-Yuan Zhang, Jun-Jun Ni, Hui Li, Zhen-Zhen Quan, Hong Qing, Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China
Juan Zhao, Aerospace Medical Center, Aerospace Center Hospital, Beijing 100049, China
Author contributions: The review was conceived and designed by Qing H, Zhao J and Zhang SY; The study was drafted by Zhang SY; The review was revised by Qing H, Zhao J and Zhang SY; The review was discussed by Qing H, Zhao J, Ni JJ, Quan ZZ, Li H and Zhang SY.
Supported by National Natural Science Foundation of China, No. 81870844, No. 82001167 and No. 82101394.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Qing, MD, PhD, Professor, Key Laboratory of Molecular Medicine and Biotherapy in the Ministry of Industry and Information Technology, Department of Biology, School of Life Science, Beijing Institute of Technology, No. 5 Yard, Zhong Guan Cun South Street, Haidian District, Beijing 100081, China. hqing@bit.edu.cn
Received: December 10, 2021
Peer-review started: December 10, 2021
First decision: March 13, 2022
Revised: April 7, 2022
Accepted: May 28, 2022
Article in press: May 28, 2022
Published online: June 26, 2022
Abstract

Over the past few decades, high-throughput screening (HTS) has made great contributions to new drug discovery. HTS technology is equipped with higher throughput, minimized platforms, more automated and computerized operating systems, more efficient and sensitive detection devices, and rapid data processing systems. At the same time, in vitro neurogenesis is gradually becoming important in establishing models to investigate the mechanisms of neural disease or developmental processes. However, challenges remain in generating more mature and functional neurons with specific subtypes and in establishing robust and standardized three-dimensional (3D) in vitro models with neural cells cultured in 3D matrices or organoids representing specific brain regions. Here, we review the applications of HTS technologies on in vitro neurogenesis, especially aiming at identifying the essential genes, chemical small molecules and adaptive microenvironments that hold great prospects for generating functional neurons or more reproductive and homogeneous 3D organoids. We also discuss the developmental tendency of HTS technology, e.g., so-called next-generation screening, which utilizes 3D organoid-based screening combined with microfluidic devices to narrow the gap between in vitro models and in vivo situations both physiologically and pathologically.

Keywords: High-throughput screening, Stem cells, Neurogenesis, Cell differentiation, Three-dimensional cell culture, Cellular microenvironments

Core Tip: High-throughput screening (HTS) is a promising technology that can screen out targets from thousands of candidates. Here, we review the evidence that HTS could be beneficial in neurogenesis methods in various ways: The HTS method can screen out specific genes that induce neural induction, small molecules that facilitate neural differentiation, and three-dimensional microenvironments that could better modulate the microenvironments in vivo. We also focus on the application and prospects of HTS in in vitro neurogenesis, as organoid-based and microfluidic platforms are needed for future research.