Role of an active reserve stem cell subset of enteroendocrine cells in intestinal stem cell dynamics and the genesis of small intestinal neuroendocrine tumors.
Role of an active reserve stem cell subset of enteroendocrine cells in intestinal stem cell dynamics and the genesis of small intestinal neuroendocrine tumors.
复制标题
肠内分泌细胞的活性储备干细胞亚群在肠干细胞动力学和小肠神经内分泌肿瘤发生中的作用。
DOI：
10.1152/ajpgi.00278.2020
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Wank,StephenA
中科院分区：
文献类型：
--
作者：
Sei,Yoshitatsu;Feng,Jianying;Zhao,Xilin;Wank,StephenA
小肠神经内分泌肿瘤（SI-NET）是一种由肠嗜铬（EC）细胞起源的分泌降钙素的分化良好的神经内分泌肿瘤。最近的研究认识到EC细胞的一个子集是标签保留在+4位置的隐窝和功能作为储备肠干细胞。重要的是，这种+4储备EC细胞亚群不仅有助于损伤和炎症期间肠上皮的再生，而且还以恒定的速率促进基底隐窝的稳态。后一种功能表明+4EC细胞亚群通过恒定的去分化速率充当活性储备干细胞。在许多家族性SI-NET病例中观察到SI-NET的早期肿瘤形成特征为基于隐窝的EC细胞簇，表明+4活性储备EC细胞亚群是起源细胞。这种新发现的EC细胞的主动储备干细胞特性可以解释与SI-NET的发生和发展相关的独特生物学机制和过程。对+4活性储备EC细胞亚群的这种特性的认识可能为探索胃肠道和其他器官中的NET提供新的机会。
Small intestinal neuroendocrine tumors (SI-NET) are serotonin-secreting well-differentiated neuroendocrine tumors of putative enterochromaffin (EC) cell origin. Recent studies recognize a subset of EC cells that is label-retaining at the +4 position in the crypt and functions as a reserve intestinal stem cell. Importantly, this +4 reserve EC cell subset not only contributes to regeneration of the intestinal epithelium during injury and inflammation but also to basal crypt homeostasis at a constant rate. The latter function suggests that the +4 EC cell subset serves as an active reserve stem cell via a constant rate of dedifferentiation. Characterization of early tumor formation of SI-NET, observed as crypt-based EC cell clusters in many cases of familial SI-NETs, suggests that the +4 active reserve EC cell subset is the cell of origin. This newly discovered active reserve stem cell property of EC cells can account for unique biological mechanisms and processes associated with the genesis and development of SI-NETs. The recognition of this property of the +4 active reserve EC cell subset may provide novel opportunities to explore NETs in the gastrointestinal tract and other organs.