Generation of enteroendocrine cell diversity in midgut stem cell lineages
Generation of enteroendocrine cell diversity in midgut stem cell lineages
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DOI：
10.1242/dev.114959
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发表时间：
2015-02-15
期刊：
影响因子：
4.6
通讯作者：
Micchelli, Craig A.
中科院分区：
文献类型：
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作者：
Beehler-Evans, Ryan;Micchelli, Craig A.
内分泌系统介导长距离肽激素信号传导，以通过循环系统将代谢状态的变化广播到远处的靶组织。在许多动物中，肠道的弥漫性内分泌系统是最大的内分泌组织，内分泌细胞亚型的全谱尚未完全表征。在这里，我们结合联合收割机的分子作图，谱系追踪和遗传分析，在成年果蝇获得新的见解，肠内分泌细胞多样性的细胞和分子机制。神经肽激素的分布被用作基础，以产生一个高分辨率的弥漫性内分泌系统的细胞图。我们的研究表明，细胞多样性可以在两个不同的层面上看到：区域和地方。我们发现，I类和II类肠内分泌细胞可以区分局部分泌的神经肽激素的组合表达。细胞谱系追踪研究表明，I类和II类细胞来自一个共同的干细胞谱系，肽谱是一个稳定的功能，肠内分泌细胞的身份在稳态和以下挑战与肠道病原体嗜虫假单胞菌。遗传分析显示，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，在弥漫性内分泌系统中实现分泌细胞多样性的一种机制是通过个体成体干细胞谱系内的细胞-细胞信号传导相互作用。
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.