Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Am J Physiol Gastrointest Liver Physiol. 2020 Oct 1;319(4):G494-G501. doi: 10.1152/ajpgi.00278.2020. Epub 2020 Aug 26.
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.
小肠神经内分泌肿瘤（SI-NET）是一种由肠嗜铬细胞（EC）起源的、分泌血清素的分化良好的神经内分泌肿瘤。最近的研究认识到，在隐窝的+4 位置有一小部分 EC 细胞具有标记保留功能，作为肠道干细胞的储备。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的肠上皮再生，而且还以恒定的速率维持基底隐窝的稳态。后一种功能表明，+4 EC 细胞亚群通过持续的去分化来充当活跃的储备干细胞。在许多家族性 SI-NET 病例中观察到基于隐窝的 EC 细胞簇的 SI-NET 早期肿瘤形成表明，+4 活跃储备 EC 细胞亚群是起源细胞。EC 细胞的这种新发现的活跃储备干细胞特性可以解释与 SI-NET 发生和发展相关的独特生物学机制和过程。认识到+4 活跃储备 EC 细胞亚群的这种特性可能为探索胃肠道和其他器官中的 NET 提供新的机会。
