Suzuki Katsumasa, Fukui Hirokazu, Kayahara Takahisa, Sawada Mitsutaka, Seno Hiroshi, Hiai Hiroshi, Kageyama Ryoichiro, Okano Hideyuki, Chiba Tsutomu
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Biochem Biophys Res Commun. 2005 Mar 4;328(1):348-52. doi: 10.1016/j.bbrc.2004.12.174.
We have previously shown that Hes1 is expressed both in putative epithelial stem cells just above Paneth cells and in the crypt base columnar cells between Paneth cells, while Hes1 is completely absent in Paneth cells. This study was undertaken to clarify the role of Hes1 in Paneth cell differentiation, using Hes1-knockout (KO) newborn (P0) mice. Electron microscopy revealed premature appearance of distinct cells containing cytoplasmic granules in the intervillous region in Hes1-KO P0 mice, whereas those cells were absent in wild-type (WT) P0 mice. In Hes1-KO P0 mice, the gene expressions of cryptdins, exclusively present in Paneth cells, were all enhanced compared with WT P0 mice. Immunohistochemistry demonstrated increased number of both lysozyme-positive and cryptdin-4-positive cells in the small intestinal epithelium of Hes1-KO P0 mice as compared to WT P0 mice. Thus, Hes1 appears to have an inhibitory role in Paneth cell differentiation in the small intestine.
我们之前已经表明,Hes1在潘氏细胞上方的假定上皮干细胞以及潘氏细胞之间的隐窝基底柱状细胞中均有表达,而在潘氏细胞中则完全不存在。本研究利用Hes1基因敲除(KO)新生(P0)小鼠,旨在阐明Hes1在潘氏细胞分化中的作用。电子显微镜显示,Hes1-KO P0小鼠绒毛间区域出现了含有细胞质颗粒的独特细胞的过早出现,而野生型(WT)P0小鼠中则没有这些细胞。在Hes1-KO P0小鼠中,仅存在于潘氏细胞中的隐窝素的基因表达与WT P0小鼠相比均有所增强。免疫组织化学显示,与WT P0小鼠相比,Hes1-KO P0小鼠小肠上皮中溶菌酶阳性和隐窝素-4阳性细胞的数量均增加。因此,Hes1似乎在小肠潘氏细胞分化中具有抑制作用。