近日，瑞典卡罗林斯卡学院教授Ulrika Marklund及其团队的研究开发出了小鼠小肠粘膜下神经元类别的转录组、连接和发育。该研究于2025年5月29日发表于国际一流学术期刊《自然—神经科学》杂志上。

该研究团队通过单细胞RNA测序鉴定了两种假定的分泌运动神经元类别和一种以前未被识别的粘膜下固有初级传入神经元类别。利用病毒介导的每一类标记，课题组人员揭示了它们在粘膜下-粘膜背景下的形态和神经投射，发现了所有类别之间的联系以及与肠嗜铬细胞意想不到的密切联系。在出生后阶段进一步的转录组分析和谱系追踪显示，粘膜下神经丛中的神经元身份是通过神经发生时最初的二元命运分裂出现的，随后是表型多样化，类似于肌肠丛的发育过程。小组提出了一个统一的发展框架，神经元多样化跨越肠壁。他们的研究提供了对粘膜下神经元的分子、发育和形态学的全面了解，为探索粘膜下神经丛的生理功能、电路动力学和形成开辟了新的途径。

据悉，肠粘膜下丛调节必要的消化功能，但其神经元组成仍不完全了解。

附：英文原文

Title: The transcriptomes, connections and development of submucosal neuron classes in the mouse small intestine

Author: Li, Wei, Morarach, Khomgrit, Liu, Ziwei, Banerjee, Sanghita, Chen, Yanan, Harb, Ashley L., Kosareff, Joel M., Hall, Charles R., Lpez-Redondo, Fernando, Jalalvand, Elham, Mohamed, Suad H., Mikhailova, Anastassia, Linden, David R., Marklund, Ulrika

Issue&Volume: 2025-05-29

Abstract: The enteric submucosal plexus regulates essential digestive functions, yet its neuronal composition remains incompletely understood. We identified two putative secretomotor neuron classes and a previously unrecognized submucosal intrinsic primary afferent neuron class through single-cell RNA sequencing in the mouse small intestine. Using viral-mediated labeling of each class, we uncovered their morphologies and neural projections in the submucosa–mucosa context, finding connections among all classes and an unexpected close association with enterochromaffin cells. Further transcriptome analysis at the postnatal stage and lineage tracing revealed that neuron identities in the submucosal plexus emerge through an initial binary fate split at neurogenesis, followed by phenotypic diversification, akin to the developmental process of the myenteric plexus. We propose a unified developmental framework for neuronal diversification across the gut wall. Our study offers comprehensive molecular, developmental and morphological insights into submucosal neurons, opening new avenues for exploring physiological functions, circuit dynamics and formation of the submucosal plexus.

DOI: 10.1038/s41593-025-01962-x

Source: https://www.nature.com/articles/s41593-025-01962-x