Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach.

Lrig1+ gastric isthmal progenitor cells restore normal gastric lineage cells during damage recovery in adult mouse stomach.
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DOI:
10.1136/gutjnl-2017-313874
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发表时间:
2018-09
期刊:
Gut
影响因子:
24.5
通讯作者:
Powell AE
Powell AE
中科院分区:
医学1区
文献类型:
--
作者:
Choi E;Lantz TL;Vlacich G;Keeley TM;Samuelson LC;Coffey RJ;Goldenring JR;Powell AE

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Lrig1是皮肤和肠道中增殖和静止的干细胞的标志。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。我们还研究了在小鼠急性胃损伤后,表达Lrig1的祖细胞如何通过对壁细胞的谱系承诺而促进正常胃粘膜的再生。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。采用Lrig1/YFP小鼠,用DMP-777诱导急性损伤,研究Lrig1-YFP标记的细胞在损伤的胃粘膜中是否能分化为正常的胃系细胞。我们还研究了Lrig1-CreERT2/CreERT2(Lrig1基因敲除)小鼠,以检查急性损伤后胃体粘膜再生是否需要Lrig1蛋白。Lrig1-YFP标记的细胞在胃体和胃窦内都能形成胃谱系上皮细胞,与已发表的结果相反,Lgr5只在胃窦内标记前体细胞。在胃体急性氧合萎缩后的恢复期,Lrig1-YFP标记的细胞有助于修复受损的胃氧合腺。Lrig1基因缺失的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。在急性氧合萎缩后,Lrig1+峡部前体细胞对主要细胞系的转分化没有贡献。Lrig1标记胃体上皮祖细胞,通过分化为小鼠胃中的正常胃系细胞,能够重新填充受损的胃泌酸黏膜。
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. 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. 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. Lrig1 marks gastric corpus epithelial progenitor cells capable of repopulating the damaged oxyntic mucosa by differentiating into normal gastric lineage cells in mouse stomach.
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