Analysis of gastric epithelial lineage

小鼠胃单位中存在的自我更新上皮细胞群来自多能干细胞，并经历有序的迁移相关分化和凋亡。三种主要细胞类型（产生酸的壁细胞、产生黏液的窝细胞、胃蛋白酶原和产生内在因子的产酶细胞）的稳定状态普查是精确控制的，尽管每个谱系的迁移率有显著差异。一个转基因小鼠模型已经被创建来定义这些谱系的增殖、分化和死亡程序之间的功能相互关系。利用小鼠H^+/K^+- atp酶的非催化β亚基基因的-1035 ~ +24核苷酸，在顶壁细胞系中直接表达减毒白喉毒素A亚基。毒素使分化的壁细胞完全消融。壁细胞的损失伴随着位于胃单位增殖室的未分化无颗粒细胞数量增加5倍。成熟壁细胞的缺失也与颈前细胞分化受阻以及颈前细胞和成熟产酶细胞后代的耗竭有关。这些结果表明，成熟的壁细胞在影响胃上皮细胞前体的决策和调节与迁移相关的坑系和产酶系的终末分化程序方面处于战略地位。

The self-renewing epithelial populations present in the gastric units of the mouse stomach are descended from a multipotent stem cell and undergo an orderly migration-associated differentiation followed by apoptosis. The steady state census of the three principal cell types (acid-producing parietal cells, mucin-producing pit cells, and pepsinogen and intrinsic factor-producing zymogenic cells) is accurately controlled, despite marked differences in the rates of migration of each lineage. A transgenic mouse model has been created to define functional interrelationships between the proliferation, differentiation, and death programs of these lineages. Nucleotides -1035 to +24 of the noncatalytic β subunit gene of mouse H^+/K^+-ATPase were used to direct expression of an attenuated diphtheria toxin A subunit in the parietal cell lineage. The toxin produced complete ablation of differentiated parietal cells. Loss of parietal cells was accompanied by a 5-fold increase in the number of undifferentiated granule-free cells located in the proliferative compartment of gastruc units. Loss of mature parietal cells was also associated with a block in the differentiation of pre-neck cells and a depletion of their neck and mature zymogenic cell descendants. These results suggest that the mature parietal cell is in a strategic position to influence decision-making among gastric epithelial cell precursors and to modulate the migration-associated terminal differentiation programs of the pit and zymogenic lineages.