The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage.
The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage.
复制标题
胃上皮祖细胞生态位和酶原（主要）细胞谱系的分化。
DOI：
10.1016/j.ydbio.2008.10.025
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Mills, Jason C.
中科院分区：
文献类型：
--
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.
在哺乳动物胃肠道中，指定多个、不同谱系发育的细胞命运决定在很大程度上是由干细胞和早期谱系祖细胞与其微环境或生态位的相互作用决定的。在这里，我们表明胃壁细胞（PC）是先前未描述的胃上皮颈细胞生态位的关键细胞成分，胃上皮颈细胞是消化酶分泌酶原细胞（ZC）的祖细胞。 PC 的基因消融导致整个酶谱系的模式化失败：祖细胞显示出分化细胞标记的过早表达，并且完全分化的 ZC 未能发育。我们开发了一个单独的小鼠模型，其中 PC 不仅定位于祖细胞生态位，而且还异位定位于胃单位基底，该基底通常被终末分化的 ZC 占据。令人惊讶的是，这些错误定位的 PC 并未将相邻的酶发生谱系细胞维持在祖细胞状态，这表明 PC 虽然是必要的，但不足以定义祖细胞生态位。我们通过敲除 Mist1−/− 小鼠中的细胞骨架调节基因 Cd2ap 来诱导 PC 错误定位，从而导致 ZC 中 E-钙粘蛋白定位异常、ZC-ZC 连接不规则以及 PC 对 ZC 单层的破坏。因此，胃单元的特征组织学（PC 位于中部，ZC 位于底部）可能取决于 ZC 迁移到底部时在 ZC 中建立有序的粘附连接网络。
In the mammalian gastrointestinal tract, the cell fate decisions that specify the development of multiple, diverse lineages are governed in large part by interactions of stem and early lineage progenitor cells with their microenvironment, or niche. Here, we show that the gastric parietal cell (PC) is a key cellular component of the previously undescribed niche for the gastric epithelial neck cell, the progenitor of the digestive enzyme secreting zymogenic (chief) cell (ZC). Genetic ablation of PCs led to failed patterning of the entire zymogenic lineage: progenitors showed premature expression of differentiated cell markers, and fully differentiated ZCs failed to develop. We developed a separate mouse model in which PCs localized not only to the progenitor niche, but also ectopically to the gastric unit base, which is normally occupied by terminally differentiated ZCs. Surprisingly, these mislocalized PCs did not maintain adjacent zymogenic lineage cells in the progenitor state, demonstrating that PCs, though necessary, are not sufficient to define the progenitor niche. We induced this PC mislocalization by knocking out the cytoskeleton-regulating gene Cd2ap in Mist1−/− mice, which led to aberrant E-cadherin localization in ZCs, irregular ZC-ZC junctions, and disruption of the ZC monolayer by PCs. Thus, the characteristic histology of the gastric unit, with PCs in the middle and ZCs in the base, may depend on establishment of an ordered adherens junction network in ZCs as they migrate into the base.
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DOI：
10.1083/jcb.200706108
发表时间：
2008-03-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnson RI;Seppa MJ;Cagan RL
通讯作者：
Cagan RL
影响因子：
4.6
作者：
Jain, Renu N.;Samuelson, Linda C.
通讯作者：
Samuelson, Linda C.
影响因子：
64.5
作者：
Dustin, ML;Olszowy, MW;Shaw, AS
通讯作者：
Shaw, AS
影响因子：
15.9
作者：
BEAUCHAMP, RD;BARNARD, JA;COFFEY, RJ
通讯作者：
COFFEY, RJ
影响因子：
--
作者：
KARAM, SM;LEBLOND, CP
通讯作者：
LEBLOND, CP