Li Xing, Madison Blair B, Zacharias William, Kolterud Asa, States David, Gumucio Deborah L
Bioinformatics Program, Departments of Cell and Developmental Biology and Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-2200, USA.
Physiol Genomics. 2007 May 11;29(3):290-301. doi: 10.1152/physiolgenomics.00269.2006. Epub 2007 Feb 13.
Reciprocal cross talk between the endodermally derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation of the developing mammalian intestine. Though both epithelium and mesenchyme participate in patterning, the mesenchyme is thought to play a prominent role in the determination of the epithelial phenotype during development and in adult life. However, the molecular basis for this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in the separate mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble inhibitors and modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf, and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional cross talk. We also catalog the most highly enriched transcription factors in both compartments. The results bolster previous evidence suggesting a major role for Hnf4gamma and Hnf4alpha in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue restricted in their expression, mesenchymally enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely nontissue specific.
内胚层来源的上皮细胞与下方间充质之间的相互串扰对于发育中的哺乳动物肠道的区域模式形成和正常分化是必需的。尽管上皮细胞和间充质都参与模式形成，但间充质被认为在发育过程中和成年期上皮表型的决定中起主要作用。然而，这种指导性优势的分子基础尚不清楚。事实上，令人惊讶的是，对于许多关键信号分子的细胞起源以及它们所影响的基因转录事件知之甚少。在这里，我们分析了围产期小鼠肠道中分别在间充质和上皮区室中表达的基因。数据表明，绝大多数信号通路（如刺猬信号通路、骨形态发生蛋白信号通路、Wnt信号通路、成纤维细胞生长因子信号通路和胰岛素样生长因子信号通路）的可溶性抑制剂和调节剂主要或仅由间充质表达，这解释了其在指导性串扰中占主导地位的能力。我们还编目了两个区室中最高度富集的转录因子。结果支持了先前的证据，表明肝细胞核因子4γ和肝细胞核因子4α在上皮基因调控中起主要作用。最后，我们发现，虽然上皮富集的基因往往在表达上具有高度的组织限制性，但间充质富集的基因往往在多种组织中广泛表达。因此，表征肠道上皮的独特组织特异性特征是由间充质指导和支持的，间充质自身表达的基因在很大程度上是非组织特异性的。
