2023年10月20日，来自美国罗格斯大学Michael P. Verzi等研究人员合作在学术期刊《细胞—干细胞》发表了标题为“TGFB1 induces fetal reprogramming and enhances intestinal regeneration.”的研究成果，发现TGFB1诱导胎儿重编程并促进肠道再生。
研究人员表示，肠道上皮具有从损伤中恢复的非凡能力。
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。
Highlights
- TGFB1 signaling is required for epithelial regeneration following irradiation
- TGFB1 promotes fetal reversion in intestinal organoid cultures
- TGFB1 induces a YAP-SOX9 regenerative circuit
- TGFB1-pre-treated organoids enhance engraftment efficiency into damaged colon
Summary
The gut epithelium has a remarkable ability to recover from damage. We employed a combination of high-throughput sequencing approaches, mouse genetics, and murine and human organoids and identified a role for TGFB signaling during intestinal regeneration following injury. At 2 days following irradiation (IR)-induced damage of intestinal crypts, a surge in TGFB1 expression is mediated by monocyte/macrophage cells at the location of damage. The depletion of macrophages or genetic disruption of TGFB signaling significantly impaired the regenerative response. Intestinal regeneration is characterized by the induction of a fetal-like transcriptional signature during repair. In organoid culture, TGFB1 treatment was necessary and sufficient to induce the fetal-like/regenerative state. Mesenchymal cells were also responsive to TGFB1 and enhanced the regenerative response. Mechanistically, pro-regenerative factors, YAP/TEAD and SOX9, are activated in the epithelium exposed to TGFB1. Finally, pre-treatment with TGFB1 enhanced the ability of primary epithelial cultures to engraft into damaged murine colon, suggesting promise for cellular therapy.
文章来源：
Lei Chen, Xia Qiu, Abigail Dupre et al,TGFB1 induces fetal reprogramming and enhances intestinal regeneration.DOI: 10.1016/j.stem.2023.09.015，Cell Stem Cell：最新IF：25.269
