Objective Lrig1 is a marker of proliferative and quiescent stem cells in the skin and intestine. We examined whether Lrig1-expressing cells are long-lived gastric progenitors in gastric glands in the mouse stomach. We also investigated how the Lrig1-expressing progenitor cells contribute to the regeneration of normal gastric mucosa by lineage commitment to parietal cells after acute gastric injury in mice. Design We performed lineage labelling using Lrig1-CreERT2/+;R26R-YFP/+ (Lrig1/YFP) or R26R-LacZ/+ (Lrig1/LacZ) mice to examine whether the Lrig1-YFP-marked cells are gastric progenitor cells. We studied whether Lrig1-YFP-marked cells give rise to normal gastric lineage cells in damaged mucosa using Lrig1/YFP mice after treatment with DMP-777 to induce acute injury. We also studied Lrig1-CreERT2/CreERT2 (Lrig1 knockout) mice to examine whether the Lrig1 protein is required for regeneration of gastric corpus mucosa after acute injury. Results Lrig1-YFP-marked cells give rise to gastric lineage epithelial cells both in the gastric corpus and antrum, in contrast to published results that Lgr5 only marks progenitor cells within the gastric antrum. Lrig1-YFP-marked cells contribute to replacement of damaged gastric oxyntic glands during the recovery phase after acute oxyntic atrophy in the gastric corpus. Lrig1 null mice recovered normally from acute gastric mucosal injury indicating that Lrig1 protein is not required for lineage differentiation. Lrig1+ isthmal progenitor cells did not contribute to transdifferentiating chief cell lineages after acute oxyntic atrophy. Conclusions Lrig1 marks gastric corpus epithelial progenitor cells capable of repopulating the damaged oxyntic mucosa by differentiating into normal gastric lineage cells in mouse stomach.

中文翻译：

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Lrig1+胃峡部祖细胞在成年小鼠胃损伤恢复过程中恢复正常胃谱系细胞

目的 Lrig1 是皮肤和肠道中增殖和静止干细胞的标志物。我们检查了表达 Lrig1 的细胞是否是小鼠胃中胃腺中的长寿胃祖细胞。我们还研究了表达 Lrig1 的祖细胞如何在小鼠急性胃损伤后通过对壁细胞的谱系定向促进正常胃粘膜的再生。设计 我们使用 Lrig1-CreERT2/+；R26R-YFP/+ (Lrig1/YFP) 或 R26R-LacZ/+ (Lrig1/LacZ) 小鼠进行谱系标记，以检查 Lrig1-YFP 标记的细胞是否是胃祖细胞。我们使用 Lrig1/YFP 小鼠研究了 Lrig1-YFP 标记的细胞是否在用 DMP-777 治疗诱导急性损伤后在受损粘膜中产生正常的胃谱系细胞。我们还研究了 Lrig1-CreERT2/CreERT2（Lrig1 敲除）小鼠，以检查急性损伤后胃体粘膜再生是否需要 Lrig1 蛋白。结果 Lrig1-YFP 标记的细胞在胃体和胃窦中产生胃谱系上皮细胞，与已发表的结果相反，Lgr5 仅标记胃窦内的祖细胞。Lrig1-YFP 标记的细胞有助于在胃体急性泌酸萎缩后的恢复阶段更换受损的胃泌酸腺。Lrig1 缺失小鼠从急性胃粘膜损伤中恢复正常，表明 Lrig1 蛋白不是谱系分化所必需的。Lrig1+ 峡部祖细胞在急性泌酸萎缩后对主细胞谱系的转分化没有贡献。