TFF2 mRNA transcript expression marks a gland progenitor cell of the gastric oxyntic mucosa.

TFF2 mRNA transcript expression marks a gland progenitor cell of the gastric oxyntic mucosa.
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DOI:
10.1053/j.gastro.2010.08.003
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发表时间:
2010-12
期刊:
影响因子:
29.4
通讯作者:
Wang TC
Wang TC
中科院分区:
医学1区
文献类型:
--
作者:
Quante M;Marrache F;Goldenring JR;Wang TC

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胃干细胞位于胃腺峡部,并产生上皮祖细胞,其经历双极迁移并分化为胃小凹和泌酸谱系。虽然位于峡部下方的胃粘液颈细胞表达三叶因子家族2(TFF 2)蛋白,但TFF 2 mRNA转录物集中在正常粘膜体颈部以上的细胞中,表明TFF 2转录是胃祖细胞的标志物。使用BAC策略,我们产生了具有TFF 2启动子控制下的他莫昔芬诱导型Cre的转基因小鼠(TFF 2-BAC-CreERT 2),并分析了来自TFF 2 mRNA转录表达(TTE)细胞的谱系衍生。TTE细胞定位于峡部,高于并不同于TFF 2蛋白表达粘液颈细胞。谱系追踪显示,这些细胞在20天内向腺体底部迁移,产生壁细胞、粘液颈细胞和主细胞,但不产生ECL细胞。表面粘液细胞不是来源于TTE细胞,TTE谱系的后代不能存活超过200天。TTE细胞位于峡部邻近Dclk 1+推定的祖细胞。诱导痉挛性多肽表达化生(SPEM)与ESTA-777诱导的急性壁细胞损失表明,这种化生表型可能会出现部分通过转分化的主细胞,而不是扩张的粘液颈或祖细胞。TFF 2转录表达细胞是粘液颈,壁和酶原的祖细胞,但不是胃泌酸粘膜中的小凹或ECL细胞系。
Gastric stem cells are located in the isthmus of the gastric glands, and give rise to epithelial progenitors that undergo bipolar migration and differentiation into pit and oxyntic lineages. While gastric mucus neck cells, located below the isthmus, express trefoil factor family 2 (TFF2) protein, TFF2 mRNA transcripts are concentrated in cells above the neck region in normal corpus mucosa, suggesting that TFF2 transcription is a marker of gastric progenitor cells. Using a BAC strategy, we generated a transgenic mouse with a tamoxifen-inducible Cre under the control of the TFF2 promoter (TFF2-BAC-CreERT2) and analyzed the lineage derivation from TFF2 mRNA transcript-expressing (TTE) cells. TTE cells were localized to the isthmus, above and distinct from TFF2 protein-expressing mucus neck cells. Lineage tracing revealed that these cells migrated towards the bottom of the gland within 20 days, giving rise to parietal, mucous neck and chief cells, but not to ECL cells. Surface mucus cells were not derived from TTE cells, and the progeny of the TTE lineage did not survive beyond 200 days. TTE cells were localized in the isthmus adjacent to Dclk1+ putative progenitor cells. Induction of spasmolytic polypeptide-expressing metaplasia (SPEM) with DMP-777-induced acute parietal cell loss revealed that this metaplastic phenotype might arise in part through transdiferentiation of chief cells as opposed to expansion of mucus neck or progenitor cells. TFF2-transcript-expressing cells are progenitors for mucus neck, parietal and zymogenic, but not for pit or ECL cell lineages in the oxyntic gastric mucosa.
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