Molecular characterization of mouse gastric zymogenic cells
Molecular characterization of mouse gastric zymogenic cells
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DOI：
10.1074/jbc.m308385200
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发表时间：
2003-11-14
影响因子：
4.8
通讯作者：
Gordon, JI
中科院分区：
文献类型：
--
作者：
Mills, JC;Andersson, N;Gordon, JI
产酶细胞（ZC）、产酸壁细胞（PC）和分泌粘液的小凹细胞是成年小鼠和人类胃中的主要上皮细胞系。每个谱系都来源于多能胃干细胞，并在离散的粘膜内陷（胃单位）内经历永久更新。在这份报告中，我们分析了ZCs的分子特征及其对胃上皮稳态的贡献。基因芯片分析产生了一个数据集的57个mRNA编码已知的蛋白质和14个EST丰富的成年小鼠ZCs。该数据集，从比较纯化的细胞群体的逆流淘洗和凝集素淘选，进行了验证，通过实时定量逆转录-PCR研究选定的基因的体内表达，使用细胞收获从不同地区的胃单位的激光捕获显微切割。富含ZC的mRNA包括血管生成的调节剂（例如血小板衍生生长因子A和B）。由于PC富含编码其他血管生成因子（例如Vegfb）的转录物，因此通过对两种类型小鼠中胃单位周围的毛细血管网络进行定量三维成像来检查这两种谱系对血管发育的贡献。在正常成年无菌FVB/N动物中，位于胃近端（胃体）区域的含ZC和PC单元的网络密度平均比位于远端（胃窦）区域的缺乏这些谱系的单元高2倍（p < 0.01）。与正常同窝仔的胃体单元相比，具有所有ZC和PC的工程化消融的无菌转基因小鼠在其胃体区域单元中的毛细血管网络密度降低2倍（p < 0.01）。这些结果支持了一个新兴的主题，即成年小鼠肠道中的血管生成是由其上皮谱系和底层间充质之间的串扰调制的。
Zymogenic cells (ZCs), acid-producing parietal cells (PCs), and mucus-secreting pit cells are the principal epithelial lineages in the stomachs of adult mice and humans. Each lineage is derived from the multipotent gastric stem cell and undergoes perpetual renewal within discrete mucosal invaginations (gastric units). In this report, we analyze the molecular features of ZCs and their contributions to gastric epithelial homeostasis. GeneChip analysis yielded a dataset of 57 mRNAs encoding known proteins and 14 ESTs enriched in adult mouse ZCs. This dataset, obtained from comparisons of cellular populations purified by counterflow elutriation and lectin panning, was validated by real-time quantitative reverse transcription-PCR studies of the in vivo expression of selected genes using cells harvested from different regions of gastric units by laser capture microdissection. ZC-enriched mRNAs include regulators of angiogenesis (e.g. platelet-derived growth factors A and B). Because PCs are enriched in transcripts encoding other angiogenic factors (e.g. Vegfb), the contributions of these two lineages to vascular development was examined by performing quantitative three-dimensional imaging of the capillary networks that surround gastric units in two types of mice. In normal adult gnotobiotic FVB/N animals, network density is on average 2-fold higher in ZC- and PC-containing units located in the proximal (corpus) region of the stomach compared with units positioned in the distal (antral) region that lack these lineages (p < 0.01). Gnotobiotic transgenic mice with an engineered ablation of all ZCs and PCs have a 2-fold reduction in capillary network density in their corpus region gastric units compared with the corpus units of normal littermates (p < 0.01). These results support an emerging theme that angiogenesis in the adult mouse gut is modulated by cross-talk between its epithelial lineages and the underlying mesenchyme.