Kallyope公司Paul A. Muller团队取得一项新突破。他们开发出肠道神经元的体内转录组学、功能、电路基础和翻译分析。该研究于2025年12月16日发表于国际一流学术期刊《细胞》杂志上。

为了在药物发现中实现靶标识别和验证，该团队利用了一套现代神经科学工具并对ENs进行了分析。单核测序、化学遗传学、电路追踪和药理学解决了EN群体如何调节胃肠道运动、分泌、食物摄入和炎症。然后，该团队确定了小鼠和人类EN亚群之间的保护程度。这项工作为EN细胞类型和区域特异性功能提供了与疾病相关的见解，为进一步探索EN在体内的功能奠定了方法学基础，并强调了小鼠和人类之间的翻译障碍和机遇。

据了解，肠神经元（ENs）与胃肠道（GI）相互交织，在胃肠道中整合局部和外部信息，以协调不同细胞类型的肠道功能。由于EN功能障碍是多种胃肠道疾病病理生理学的基础，因此针对相关的EN人群提出了一种多方面的治疗方法。尽管它们在基本生理学中很重要，但从转录、基于电路和功能的角度来看，ENs仍未得到充分的探索。

附：英文原文

Title: In vivo transcriptomic, functional, circuit-based, and translational analyses of enteric neurons

Author: Claire J. Millett, James J. Shaver, Bernadette Bracken, Sunny J. Jones, Robert J. Lovelett, Dave A. Rubinow, Rijul Singhal, Celia Charlton, Nadine Piazza, Quinn Hauck, Nikhil Sharma, Paul A. Muller

Issue&Volume: 2025-12-16

Abstract: Enteric neurons (ENs) are interwoven into the gastrointestinal (GI) tract, where they integrate local and external information to coordinate gut function across diverse cell types. Since EN dysfunction underlies the pathophysiology of multiple GI diseases, targeting relevant EN populations presents a multifaceted therapeutic approach. Despite their importance in essential physiologies, ENs remain underexplored from a transcriptional, circuit-based, and functional perspective. To enable target identification and validation in drug discovery, we leveraged a suite of modern neuroscience tools and profiled ENs. Single-nuclei sequencing, chemogenetics, circuit tracing, and pharmacology resolved how EN populations can modulate GI motility, secretion, food intake, and inflammation. We then determined the extent of conservation between mouse and human EN subsets. This work provides disease-relevant insights into EN cell type- and region-specific functions, lays the methodological groundwork to further probe EN function in vivo, and highlights translational hurdles and opportunities between mouse and human.

DOI: 10.1016/j.cell.2025.11.024

Source: https://www.cell.com/cell/abstract/S0092-8674(25)01359-5