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Lrig1+ 胃峡部祖细胞在成年鼠胃损伤恢复过程中恢复正常胃谱系细胞。

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

机构信息

Nashville VA Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

出版信息

Gut. 2018 Sep;67(9):1595-1605. doi: 10.1136/gutjnl-2017-313874. Epub 2017 Aug 16.

DOI:10.1136/gutjnl-2017-313874
PMID:28814482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5815959/
Abstract

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/YFP) or (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- (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.

摘要

目的

Lrig1 是皮肤和肠道中增殖和静止干细胞的标志物。我们研究了 Lrig1 表达细胞是否是小鼠胃胃腺中的长寿胃前体细胞。我们还研究了 Lrig1 表达祖细胞如何通过向壁细胞谱系分化来促进正常胃黏膜的再生，在小鼠急性胃损伤后。

设计

我们使用 （Lrig1/YFP）或 （Lrig1/LacZ）小鼠进行谱系标记，以检查 Lrig1-YFP 标记的细胞是否为胃前体细胞。我们研究了在使用 DMP-777 诱导急性损伤后，Lrig1/YFP 小鼠中 Lrig1-YFP 标记的细胞是否能产生正常的胃谱系细胞。我们还研究了 Lrig1-（Lrig1 敲除）小鼠，以检查 Lrig1 蛋白是否是急性损伤后胃体黏膜再生所必需的。

结果

Lrig1-YFP 标记的细胞在胃体和胃窦中均产生胃谱系上皮细胞，与之前的研究结果相反，Lgr5 仅标记胃窦中的前体细胞。Lrig1-YFP 标记的细胞有助于在胃体急性萎缩后的恢复阶段替代受损的胃泌素腺。Lrig1 敲除小鼠从急性胃黏膜损伤中正常恢复，表明 Lrig1 蛋白不是谱系分化所必需的。Lrig1+峡部祖细胞在急性胃泌素萎缩后不会促进主细胞谱系的转分化。

结论

Lrig1 标记胃体上皮前体细胞，能够通过分化为正常的胃谱系细胞来重新填充受损的胃泌素黏膜，在小鼠胃中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/5b9bc3085a08/nihms918175f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/fc62926ccb46/nihms918175f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/2bcfc006ca4a/nihms918175f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/5937283ceb3f/nihms918175f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/d701e05d16bb/nihms918175f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/5b9bc3085a08/nihms918175f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/9d738d9e940e/nihms918175f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/1ac30b48a186/nihms918175f2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b043/5815959/5b9bc3085a08/nihms918175f8.jpg

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