Functional maturation of enteric neurons derived from human induced pluripotent stem cells.

IF 5.6 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Reports Pub Date : 2026-07-14 Epub Date: 2026-06-04 DOI:10.1016/j.stemcr.2026.102942

Eve S Rowland, Maciej Daniszewski, Caio Seguin, Maria A Di Biase, Gunes S Yildiz, Atefeh Namipashaki, Alice Pébay, Faranak Fattahi, Lincon A Stamp, Marlene M Hao

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Abstract

The enteric nervous system (ENS) plays a crucial role in regulating gastrointestinal function, including motility, secretion, and absorption. Enteric neurons and glia derived from human induced pluripotent stem cells (iPSCs) have vast applications in disease modeling, drug screening, and cell replacement therapy, yet our understanding of their functional maturation remains limited. Using a defined protocol for the generation of iPSC-derived enteric neurons, we examined neuronal differentiation with immunohistochemistry, gene expression analysis, and cellular-resolution calcium (Ca²⁺) imaging from day (D)21 to D57 of differentiation. By D21, cells expressing pan-neuronal markers were present, and at D22 the cultures were responsive to K⁺-induced depolarization as well as neurotransmitter receptor agonists, with maturation of responses to high K⁺ depolarization during the differentiation period. In addition, the development of spontaneous neuronal network activity was observed at 2 months post-differentiation. Together these findings provide a timeline of the functional maturation of iPSC-derived ENS cells.

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人诱导多能干细胞肠神经元的功能成熟。

肠神经系统（ENS）在调节胃肠功能，包括运动、分泌和吸收方面起着至关重要的作用。来源于人诱导多能干细胞（iPSCs）的肠神经元和胶质细胞在疾病建模、药物筛选和细胞替代治疗中有着广泛的应用，但我们对其功能成熟的了解仍然有限。使用一种确定的方案来产生ipsc衍生的肠内神经元，我们通过免疫组织化学、基因表达分析和细胞分辨率钙（Ca2+）成像来检测神经元分化，从分化的第21天到第57天。D21时，细胞表达泛神经元标记物，在D22时，培养物对K+诱导的去极化和神经递质受体激动剂有反应，在分化期间对高K+去极化的反应成熟。此外，分化后2个月观察自发神经网络活动的发展。总之，这些发现提供了ipsc衍生的ENS细胞功能成熟的时间表。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY

CiteScore

10.50

自引率

1.70%

发文量

200

审稿时长

28 weeks

期刊介绍： Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.