Beehler-Evans Ryan, Micchelli Craig A
Washington University School of Medicine, Department of Developmental Biology, 660 South Euclid Avenue, St Louis, MO 63110, USA.
Washington University School of Medicine, Department of Developmental Biology, 660 South Euclid Avenue, St Louis, MO 63110, USA
Development. 2015 Feb 15;142(4):654-64. doi: 10.1242/dev.114959.
The endocrine system mediates long-range peptide hormone signaling to broadcast changes in metabolic status to distant target tissues via the circulatory system. In many animals, the diffuse endocrine system of the gut is the largest endocrine tissue, with the full spectrum of endocrine cell subtypes not yet fully characterized. Here, we combine molecular mapping, lineage tracing and genetic analysis in the adult fruit fly to gain new insight into the cellular and molecular mechanisms governing enteroendocrine cell diversity. Neuropeptide hormone distribution was used as a basis to generate a high-resolution cellular map of the diffuse endocrine system. Our studies show that cell diversity is seen at two distinct levels: regional and local. We find that class I and class II enteroendocrine cells can be distinguished locally by combinatorial expression of secreted neuropeptide hormones. Cell lineage tracing studies demonstrate that class I and class II cells arise from a common stem cell lineage and that peptide profiles are a stable feature of enteroendocrine cell identity during homeostasis and following challenge with the enteric pathogen Pseudomonas entomophila. Genetic analysis shows that Notch signaling controls the establishment of class II cells in the lineage, but is insufficient to reprogram extant class I cells into class II enteroendocrine cells. Thus, one mechanism by which secretory cell diversity is achieved in the diffuse endocrine system is through cell-cell signaling interactions within individual adult stem cell lineages.
内分泌系统介导长距离的肽类激素信号传导，通过循环系统将代谢状态的变化传递给远处的靶组织。在许多动物中，肠道的弥散内分泌系统是最大的内分泌组织，其内分泌细胞亚型的全貌尚未完全明确。在这里，我们结合成年果蝇的分子图谱绘制、谱系追踪和遗传分析，以深入了解控制肠内分泌细胞多样性的细胞和分子机制。以神经肽激素分布为基础，生成了弥散内分泌系统的高分辨率细胞图谱。我们的研究表明，细胞多样性体现在两个不同层面：区域层面和局部层面。我们发现，I类和II类肠内分泌细胞可通过分泌性神经肽激素的组合表达在局部进行区分。细胞谱系追踪研究表明，I类和II类细胞起源于共同的干细胞谱系，并且在稳态以及受到肠道病原体嗜虫假单胞菌攻击后，肽谱是肠内分泌细胞身份的一个稳定特征。遗传分析表明，Notch信号传导控制谱系中II类细胞的建立，但不足以将现存的I类细胞重编程为II类肠内分泌细胞。因此，弥散内分泌系统实现分泌细胞多样性的一种机制是通过单个成体干细胞谱系内的细胞间信号相互作用。
