美国罗格斯大学Michael P. Verzi等研究人员合作发现，TGFB1诱导胎儿重编程并促进肠道再生。2023年10月20日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

研究人员结合使用了高通量测序方法、小鼠遗传学以及小鼠和人类器官组织，确定了TGFB信号在损伤后肠道再生过程中的作用。在辐照（IR）诱导的肠隐窝损伤后2天，单核细胞/巨噬细胞在损伤位置介导了TGFB1表达的激增。巨噬细胞的耗竭或TGFB信号转导的基因干扰会显著影响再生反应。肠道再生的特点是在修复过程中诱导类似胎儿的转录特征。在类器官培养中，TGFB1处理是诱导类胎儿/再生状态的必要且充分条件。间充质细胞也对TGFB1有反应，并增强了再生反应。

从机理上讲，在暴露于TGFB1的上皮细胞中，促再生因子YAP/TEAD和SOX9被激活。最后，TGFB1的预处理增强了原代上皮细胞培养物移植到受损小鼠结肠的能力，并为细胞疗法带来了希望。

研究人员表示，肠道上皮具有从损伤中恢复的非凡能力。

附：英文原文

Title: TGFB1 induces fetal reprogramming and enhances intestinal regeneration

Author: Lei Chen, Xia Qiu, Abigail Dupre, Oscar Pellon-Cardenas, Xiaojiao Fan, Xiaoting Xu, Prateeksha Rout, Katherine D. Walton, Joseph Burclaff, Ruolan Zhang, Wenxin Fang, Rachel Ofer, Alexandra Logerfo, Kiranmayi Vemuri, Sheila Bandyopadhyay, Jianming Wang, Gaetan Barbet, Yan Wang, Nan Gao, Ansu O. Perekatt, Wenwei Hu, Scott T. Magness, Jason R. Spence, Michael P. Verzi

Issue&Volume: 2023-10-20

Abstract: The gut epithelium has a remarkable ability to recover from damage. We employed acombination of high-throughput sequencing approaches, mouse genetics, and murine andhuman organoids and identified a role for TGFB signaling during intestinal regenerationfollowing injury. At 2 days following irradiation (IR)-induced damage of intestinalcrypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at thelocation of damage. The depletion of macrophages or genetic disruption of TGFB signalingsignificantly impaired the regenerative response. Intestinal regeneration is characterizedby the induction of a fetal-like transcriptional signature during repair. In organoidculture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerativestate. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerativeresponse. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activatedin the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced theability of primary epithelial cultures to engraft into damaged murine colon, suggestingpromise for cellular therapy.

DOI: 10.1016/j.stem.2023.09.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(23)00362-4