中国科学技术大学潘文课题组近日取得一项新成果。经过不懈努力，他们发现了VIPR1作为肠道神经检查点抑制肠道干细胞驱动的上皮再生并加剧结肠炎。2026年2月23日出版的《细胞—干细胞》杂志发表了这项成果。

该研究团队确定了损伤期间直接抑制ISC再生输出的神经元检查点。该研究组发现产生血管活性肠肽（VIP）的肠神经元直接通过上皮受体VIP受体1（VIPR1）向ISCs发出信号。在稳态下，VIP-VIPR1信号通过参与细胞外信号调节激酶(ERK)-Notum-Wnt/β-catenin抑制轴抑制ISC过度增殖。在结肠炎期间，VIPergic神经元在溃疡区域内扩张并放大该通路，从而抑制ISC驱动的再生并加剧上皮损伤。在上皮细胞或ISCs中选择性删除Vipr1可以释放这种神经元制动，恢复早期再生活性，并显着减轻结肠炎。VIP-VIPR1信号通路的ISC抑制功能在人肠道模型中是保守的。总之，这些发现将VIPR1定义为限制ISC驱动的上皮再生的ISC固有神经元检查点，并强调上皮VIPR1阻断是增强结肠炎粘膜再生的潜在策略。

据了解，肠干细胞（ISCs）驱动上皮细胞更新和再生，但神经线索如何塑造ISC行为尚不清楚。

附：英文原文

Title: VIPR1 acts as an enteric neural checkpoint that suppresses intestinal stem cell-driven epithelial regeneration and exacerbates colitis

Author: Chaoliang Li, Haohao Wang, Panrui Zhang, Jianbo Yang, Chao Ye, Xiaowei Wei, Yuchen Zhou, Zhentao Yang, Dan Cao, Kaiguang Zhang, Rongbin Zhou, Shu Zhu, Wen Pan

Issue&Volume: 2026-02-23

Abstract: Intestinal stem cells (ISCs) drive epithelial renewal and regeneration, yet how neural cues shape ISC behavior remains unclear. Here, we identify a neuronal checkpoint that directly restrains ISC regenerative output during injury. We show that vasoactive intestinal peptide (VIP)-producing enteric neurons directly signal to ISCs through the epithelial receptor VIP receptor 1 (VIPR1). In steady state, VIP-VIPR1 signaling restrains ISC hyperproliferation by engaging an extracellular signal-regulated kinase (ERK)-Notum-Wnt/β-catenin inhibitory axis. During colitis, VIPergic neurons expand within the ulcerated regions and amplify this pathway, thereby suppressing ISC-driven regeneration and exacerbating epithelial injury. Selective deletion of Vipr1 in the epithelium or in ISCs releases this neuronal brake, restores early regenerative activity, and markedly alleviates colitis. The ISC-suppressive function of VIP-VIPR1 signaling is conserved in human intestinal models. Together, these findings define VIPR1 as an ISC-intrinsic neuronal checkpoint that restricts ISC-driven epithelial regeneration and highlight epithelial VIPR1 blockade as a potential strategy to enhance mucosal regeneration in colitis.

DOI: 10.1016/j.stem.2026.01.009

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(26)00032-9