小柯机器人

澳大利亚莫纳什大学Helen E. Abud、Thierry Jardé等研究人员合作发现，间质微环境产生的神经调节蛋白1驱动肠道干细胞的增殖以及受损上皮的再生。这一研究成果于2020年7月20日在线发表在《细胞—干细胞》上。

据研究人员介绍，表皮生长因子（EGF）维持肠道干细胞（ISC）增殖，是类器官生长培养基的关键组成部分，但对于肠道动态平衡却是不可或缺的，这表明多种EGF家族配体在ISC功能中的作用。

研究人员发现，神经调节蛋白1（NRG1）是关键的EGF家族配体，在损伤后驱动组织修复。NRG1，而非EGF，在受损时被上调，并在间充质基质细胞、巨噬细胞和潘氏细胞中表达。NRG1敲除减少了肠道隐窝的增殖并损害再生能力。NRG1强烈刺激隐窝的增殖并诱导类器官的出芽，部分原因是通过丝裂原激活的蛋白激酶（MAPK）和AKT的升高和持续激活。同样，NRG1处理可诱导增殖性基因特征，并促进祖细胞形成类器官、增强损伤后的再生。

这些数据表明，间充质来源的NRG1是组织再生的有效介导因子，并可能有助于开发损伤后肠修复的疗法。

附：英文原文

Title: Mesenchymal Niche-Derived Neuregulin-1 Drives Intestinal Stem Cell Proliferation and Regeneration of Damaged Epithelium

Author: Thierry Jardé, Wing Hei Chan, Fernando J. Rossello, Tanvir Kaur Kahlon, Mandy Theocharous, Teni Kurian Arackal, Tracey Flores, Mégane Giraud, Elizabeth Richards, Eva Chan, Genevieve Kerr, Rebekah M. Engel, Mirsada Prasko, Jacqueline F. Donoghue, Shin-ichi Abe, Toby J. Phesse, Christian M. Nefzger, Paul J. McMurrick, David R. Powell, Roger J. Daly, Jose M. Polo, Helen E. Abud

Issue&Volume: 2020-07-20

Abstract: Epidermal growth factor (EGF) maintains intestinal stem cell (ISC) proliferation andis a key component of organoid growth media yet is dispensable for intestinal homeostasis,suggesting roles for multiple EGF family ligands in ISC function. Here, we identifiedneuregulin 1 (NRG1) as a key EGF family ligand that drives tissue repair followinginjury. NRG1, but not EGF, is upregulated upon damage and is expressed in mesenchymalstromal cells, macrophages, and Paneth cells. NRG1 deletion reduces proliferationin intestinal crypts and compromises regeneration capacity. NRG1 robustly stimulatesproliferation in crypts and induces budding in organoids, in part through elevatedand sustained activation of mitogen-activated protein kinase (MAPK) and AKT. Consistently,NRG1 treatment induces a proliferative gene signature and promotes organoid formationfrom progenitor cells and enhances regeneration following injury. These data suggestmesenchymal-derived NRG1 is a potent mediator of tissue regeneration and may informthe development of therapies for enhancing intestinal repair after injury.

DOI: 10.1016/j.stem.2020.06.021

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30288-5

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