Department of Systems Medicine, Sakaguchi Laboratory, Keio University School of Medicine, Tokyo, Japan.
Am J Physiol Gastrointest Liver Physiol. 2013 Jun 15;304(12):G1103-16. doi: 10.1152/ajpgi.00299.2012. Epub 2013 Apr 18.
We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4⁺) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4⁺ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4⁺ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas.
我们最近鉴定了锌指和 SCAN 结构域家族 4（Zscan4），它在小鼠胚胎干细胞（ES 细胞）中瞬时表达，并调节端粒伸长和基因组稳定性。本研究旨在研究 ZSCAN4 在成年胰腺中的表达，并阐明 ZSCAN4 在组织炎症及其后续再生中的作用。我们通过免疫组织化学方法检测了人胰腺中 ZSCAN4 和其他祖细胞或分化细胞标志物的表达。本研究使用了酒精性或自身免疫性胰腺炎患者的胰腺切片，这些患者在接受维持皮质类固醇治疗之前和之后。在成人胰腺中，胰岛、腺泡、导管和椭圆形细胞中存在少量 ZSCAN4 阳性（ZSCAN4⁺）细胞。这些细胞不仅表达每个胰腺部位的分化细胞标志物，还表达其他组织干细胞/祖细胞标志物。此外，慢性胰腺炎患者的 ZSCAN4⁺细胞数量显著增加，尤其是在自身免疫性胰腺炎患者的胰腺组织中，在皮质类固醇治疗下积极再生。有趣的是，自身免疫性胰腺炎患者胰腺中的许多 ZSCAN4⁺细胞在维持皮质类固醇治疗 1 年后回到基础水平。总之，ZSCAN4 与胰腺每个部位的祖细胞标志物和分化细胞标志物的共表达可能表明成年胰腺中既有内分泌细胞又有外分泌细胞的潜能祖细胞的存在。
