Molecular characterization of mouse gastric epithelial progenitor cells
Molecular characterization of mouse gastric epithelial progenitor cells
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DOI：
10.1073/pnas.192574799
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发表时间：
2002-11-12
影响因子：
11.1
通讯作者：
Gordon, JI
中科院分区：
文献类型：
--
作者：
Mills, JC;Andersson, N;Gordon, JI
成年小鼠胃上皮在离散的解剖单元中不断更新。谱系追踪研究此前已经揭示了胃上皮谱系祖细胞（GEP）的形态特征，包括假定的多能干细胞的形态特征。然而，它们的分子特征尚未确定。在这里，我们展示了这些细胞中表达的基因和途径的分析结果。使用不需要物理破坏干细胞生态位的方法鉴定了富含 GEP 的 147 个转录物。对从该生态位中获取的激光捕获显微切割细胞进行的实时定量 RT-PCR 研究证实了 GEP 列表中选定的一组基因的富集表达。一种允许对自动注释的表达谱的功能相关性进行定量比较的算法表明，GEP 图谱与定义小鼠造血干细胞的基因数据集相似，并且与两个分化的 GEP 后代谱系（壁细胞和酶原细胞）的图谱不同。总体而言，我们的分析表明，生长因子反应途径在 GEP 中很突出，其中胰岛素样生长因子似乎发挥着关键作用。 GEP 转录物的很大一部分编码 mRNA 加工和细胞质定位所需的产物，包括卵子发生过程中轴形成所需的果蝇基因的许多同源物（例如 Y14、staufen、mago nashi）。 mRNA 靶向蛋白可能有助于这些上皮祖细胞与其微环境中的邻近细胞建立差异通讯。
The adult mouse gastric epithelium undergoes continuous renewal in discrete anatomic units. Lineage tracing studies have previously disclosed the morphologic features of gastric epithelial lineage progenitors (GEPs), including those of the presumptive multipotent stem cell. However, their molecular features have not been defined. Here, we present the results of an analysis of genes and pathways expressed in these cells. One hundred forty-seven transcripts enriched in GEPs were identified using an approach that did not require physical disruption of the stem cell niche. Real-time quantitative RT-PCR studies of laser capture microdissected cells retrieved from this niche confirmed enriched expression of a selected set of genes from the GEP list. An algorithm that allows quantitative comparisons of the functional relatedness of automatically annotated expression profiles showed that the GEP profile is similar to a dataset of genes that defines mouse hematopoietic stem cells, and distinct from the profiles of two differentiated GEP descendant lineages (parietal and zymogenic cell). Overall, our analysis revealed that growth factor response pathways are prominent in GEPs, with insulin-like growth factor appearing to play a key role. A substantial fraction of GEP transcripts encode products required for mRNA processing and cytoplasmic localization, including numerous homologs of Drosophila genes (e.g., Y14, staufen, mago nashi) needed for axis formation during oogenesis. mRNA targeting proteins may help these epithelial progenitors establish differential communications with neighboring cells in their niche.