中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (10): 4680-4689.doi: 10.4103/NRR.NRR-D-25-00630

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

诱导多能干细胞分化为特殊神经元亚型

  

  • 出版日期:2026-10-15 发布日期:2026-06-12

Advancements in differentiation of induced pluripotent stem cells into specialized neuronal subtypes

Selena Setsu1, 2, Hideyuki Okano3, Satoru Morimoto3, *   

  1. 1Laboratory of RNA Function, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan; 
    2Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan; 
    3Keio University Regenerative Medicine Research Center, Kanagawa, Japan
  • Online:2026-10-15 Published:2026-06-12
  • Contact: Satoru Morimoto, MD, PhD, satoru_morimoto@keio.jp.
  • Supported by:
    SM reports grant supports from the Japan Society for the Promotion of Science (JSPS) (KAKENHI grant Nos. JP21H05278, JP22K15736, and 22K07500, and 25H00007), the Japan Agency for Medical Research and Development (AMED) (grant Nos. JP23bm1123046 and JP23kk0305024), Daiichi Sankyo Foundation of Life Science, UBE Academic Foundation, the Kato Memorial Trust for Nambyo Research, Japan Intractable Diseases (Nanbyo) Research Foundation (2024A04), and Inamori Foundation during the conduct of the study. HO has grant supports from JSPS (KAKENHI grant Nos. JP20H00485, JP21F21410, JP21H05

摘要: https://orcid.org/0000-0003-0022-9529 (Satoru Morimoto)

Abstract: The ability to generate specialized human neurons from induced pluripotent stem cells has revolutionized neuroscience, regenerative medicine, and drug discovery. Since their discovery, induced pluripotent stem cells have emerged as an ethically favorable and versatile platform to model human neurological diseases, offering new insights beyond traditional animal models. In the past decade, rapid advances have enabled the efficient differentiation of induced pluripotent stem cells into diverse neuronal subtypes, including glutamatergic neurons, GABAergic neurons, dopaminergic neurons, serotonergic neurons, motor neurons, sensory neurons, Purkinje cells, sympathetic neurons, parasympathetic neurons, and noradrenergic neurons. Tailored combinations of developmental signaling molecules, transcription factor programming, and small molecule modulation have dramatically improved the reproducibility, scalability, and functional maturity of these differentiated neurons. These advancements are particularly timely as they underpin the next generation of disease modelling platforms, high-throughput drug screening systems, and emerging cell-based therapies for conditions such as Parkinson’s disease, amyotrophic lateral sclerosis, epilepsy, and Alzheimer’s disease. Moreover, the field is moving toward standardized, chemically defined protocols and improved validation pipelines, including electrophysiological assays and molecular profiling, to ensure the authenticity and maturity of induced pluripotent stem cell-derived neurons. Notably, recent breakthroughs in sympathetic and parasympathetic neuron derivation are expanding the scope of induced pluripotent stem cell technology into autonomic nervous system research and cardiac neuromodulation studies. However, challenges remain, including variability across induced pluripotent stem cell lines, incomplete neuronal maturation, and scalability constraints for clinical-grade applications. Addressing these hurdles through optimization of patterning cues, co-culture systems, and advanced bioprocessing strategies will be crucial to realizing the full translational potential of induced pluripotent stem cell-derived neurons. Collectively, the methodologies and developments summarized here mark a major step toward achieving faithful, efficient, and scalable generation of human neurons in vitro, laying the foundation for personalized neurology and regenerative medicine.

Key words: cell therapy, disease modelling, dopaminergic neurons, drug screening, glutamatergic neurons, induced pluripotent stem cells, motor neurons, neuronal differentiation, Purkinje cells, regenerative medicine, sensory neurons