Mature chief cells are cryptic progenitors for metaplasia in the stomach.
Mature chief cells are cryptic progenitors for metaplasia in the stomach.
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DOI：
10.1053/j.gastro.2010.09.005
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发表时间：
2010-12
期刊：
影响因子：
29.4
通讯作者：
Goldenring JR
中科院分区：
文献类型：
--
作者：
Nam KT;Lee HJ;Sousa JF;Weis VG;O'Neal RL;Finke PE;Romero-Gallo J;Shi G;Mills JC;Peek RM Jr;Konieczny SF;Goldenring JR
胃癌在病理性粘膜环境中发展，其特征为泌酸壁细胞的丧失和粘液细胞化生。事实上，粘液细胞化生被认为是胃癌的关键癌前病变。先前的研究表明，用猫螺杆菌感染小鼠或用药物ESTA-777诱导急性壁细胞损失导致一种称为痉挛性多肽表达化生（SPEM）的化生类型的出现。我们假设SPEM是由腺体基底的增殖细胞引起的，或者是由隐蔽的祖细胞引起的，或者是由成熟主细胞的转分化引起的。利用Mist 1-Cre-ERT 2的主细胞限制性表达，我们使用谱系作图来检查SPEM谱系是否来源于3个独立的模型中的主细胞，所述模型是通过ESTA-777处理、L-635处理或猫嗜血杆菌感染诱导的。用L-635处理小鼠3天导致壁细胞快速损失，诱导显著的炎性浸润，并出现SPEM。在所有3种模型中，SPEM至少部分地由主细胞的转分化发展而来。我们进一步发现，在炎症环境中的急性壁细胞损失（L-635处理）导致源自主细胞转分化的SPEM的更快速的诱导和扩增。这些研究通过谱系追踪提供了SPEM由分化的主细胞进化而来的直接证据。因此，成熟的胃主细胞具有作为隐蔽祖细胞的能力，并在粘膜损伤和炎症的情况下重新获得增殖能力。
Gastric cancer evolves in the setting of a pathologic mucosal milieu characterized by both loss of acid-secreting parietal cells and mucous cell metaplasias. Indeed, mucous cell metaplasia is considered the critical preneoplastic lesion for gastric cancer. Previous investigations have shown that infection of mice with Helicobacter felis or induction of acute parietal cell loss with the drug DMP-777 leads to the emergence of a type of metaplasia designated spasmolytic polypeptide-expressing metaplasia (SPEM). We have hypothesized that SPEM arises from proliferating cells in gland bases, either from a cryptic progenitor cell or by transdifferentiation of mature chief cells. Taking advantage of the chief cell-restricted expression of Mist1-Cre-ERT2, we used lineage mapping to examine whether SPEM lineages were derived from chief cells in 3 independent models of induction by DMP-777 treatment, L-635 treatment, or H felis infection. Treatment of mice with L-635 for 3 days led to rapid parietal cell loss, induction of a prominent inflammatory infiltrate, and emergence of SPEM. In all 3 models, SPEM developed, at least in part, from transdifferentiation of chief cells. We further found that acute parietal cell loss in the setting of inflammation (L-635 treatment) led to more rapid induction and expansion of SPEM derived from transdifferentiation of chief cells. These studies provide direct evidence by lineage tracing that SPEM evolves from differentiated chief cells. Thus, mature gastric chief cells have the ability to act as cryptic progenitors and reacquire proliferative capacity within the context of mucosal injury and inflammation.
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影响因子：
3.1
作者：
Abe, S;Sasano, H;Toyota, T
通讯作者：
Toyota, T
影响因子：
29.4
作者：
Fox, JG;Li, XT;Wang, TC
通讯作者：
Wang, TC
胃上皮祖细胞生态位和酶原（主要）细胞谱系的分化。
影响因子：
2.7
作者：
Bredemeyer, Andrew J.;Geahlen, Jessica H.;Weis, Victoria G.;Huh, Won Jae;Zinselmeyer, Bernd H.;Srivatsan, Subhashini;Miller, Mark J.;Shaw, Andrey S.;Mills, Jason C.
通讯作者：
Mills, Jason C.
影响因子：
29.4
作者：
MURAYAMA, Y;MIYAGAWA, JI;MATSUZAWA, Y
通讯作者：
MATSUZAWA, Y
影响因子：
29.4
作者：
Nomura, S;Baxter, T;Goldenring, JR
通讯作者：
Goldenring, JR