Advances in Induced Pluripotent Stem Cell Reprogramming and Its Application in Amyotrophic Lateral Sclerosis: A Review
2025
Yingliu Luo | Zhenru Xu | Zunxiong Li
ABSTRACT Since Yamanaka's landmark achievement in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) using the four key transcription factors—OCT4, SOX2, KLF4, and c‐Myc (OSKM)—iPSC technology has made significant strides. Notable advancements include refining reprogramming factors, delivery systems, somatic cell selection, and optimization of reprogramming conditions, along with developing chemical reprogramming methods. With their unparalleled proliferative capacity and near‐pluripotent differentiation potential, iPSCs have become invaluable tools for investigating neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Neuronal models derived from ALS patient‐specific iPSCs, particularly iPSC‐derived motor neurons (iPSC‐MNs), offer a robust platform to recapitulate disease‐specific pathology and investigate the molecular mechanisms underpinning ALS, thereby accelerating the discovery of novel therapeutic strategies. This review highlights the evolution of iPSC technology and its transformative applications in ALS modeling, drug discovery, and therapeutic development.
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