TTNPB Promotes Human Pluripotent Stem Cell-To-Neural Stem Cell Transition Via Modulation Of Chromatin Accessibility And The S-(5'-Adenosyl)-L-Homocysteine/Choline Metabolic Network

    February 2026 in “ Advanced Science ”
    Ruilin Du, Yudi Ren, Qiaoqiao Meng, Peng Wei, Ruyu Zhu, Junjie Bao, Ye Yang, Shuo Yan, Chao Yue, Xuebin Zhu, Shuo Cao, Chunxia Hao, Wei Sun, Yongli Song, Xihe Li, Zhimin Wu, Siqin Bao, Yanglin Chen
    TLDR TTNPB helps turn stem cells into neural stem cells, improving depression-like behaviors in rats.
    The study explores the role of TTNPB, a retinoic acid receptor agonist, in facilitating the transition of human pluripotent stem cells (PSCs) to neural stem cells (NSCs) by modulating chromatin accessibility and metabolic networks. By combining TTNPB with the Wnt activator CHIR99021, researchers successfully induced advanced neural stem cells (ANSCs) from PSCs, which showed enhanced differentiation into neural lineages. TTNPB upregulated neuroectodermal genes and downregulated pluripotency markers, indicating a strong neural fate bias. However, TTNPB alone could not maintain NSC identity without CHIR99021, emphasizing their synergistic effect. The study highlights the TTNPB-SAH/PEMT-Choline metabolic network's role in promoting neuroectodermal fate specification and suggests potential applications in regenerative therapies for neurological disorders.
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