Toward the Tissue-ome: A Map of the C. elegans Cell-specific Transcriptome

 描述(申请人提供)：多细胞生物面临的挑战是协调其所有组织的功能，以适应不断变化的营养、温度和环境，以造福于整个有机体。疾病和衰老也有组织特异性和全身性的影响。然而，组织如何在整个生物体中协调的问题目前是一个悬而未决的问题。线虫线虫的体型很简单，只有959个细胞和少量的主要组织。虽然有些组织已经得到了很好的研究，但我们对其他组织知之甚少，而且人们越来越认识到，这些较少研究的组织中的一些组织具有内分泌(激素信号)功能。具体地说，最近的证据表明，蠕虫的皮肤(皮下组织)和肠道是主要的内分泌组织，协调来自神经元的关于营养和条件的信号，并将这些信息转化为关于长寿和繁殖的决定。在我们以前的工作中，我们发现生殖衰老和躯体衰老速率是由非细胞自主决定的。然而，由于分离成线虫组织的难度较大，相关组织相对缺乏特征性。我的实验室最近解决了这个问题，开发了一种温和分离成年线虫组织的方法，使我们能够对细胞进行分类，并进行RNA-SEQ来识别动物中每种组织类型的转录组。在这个项目中，我们将使用我们的技术来获得每个组织(“组织组”)的组织特异性转录组信息，并将这些信息与计算机方法相结合，以确定活动和通信网络。我们还将使用生化方法来确定组织特异性转录因子的活性，这将使我们能够了解线虫如何整合信号，向整个动物传达代谢和长寿的决定。线虫数量少的细胞和简单的组织使其成为理想的系统，在其中不仅

 DESCRIPTION (provided by applicant): Multi-cellular organisms face the challenge of coordinating all of their tissues' functions in response to changing nutrients, temperatures, and environments for the benefit of the whole organism. Disease and aging also have effects that are both tissue-specific and systemic. However, the question of how tissues are coordinated throughout a whole organism is currently an unsolved problem. The nematode C. elegans has a simple body plan, with only 959 cells and a small number of major tissues. While some tissues have been well studied, we know less about others, and it is becoming appreciated that some of these lesser-studied tissues have endocrine (hormonal signaling) functions. Specifically, recent evidence suggests that the worm's skin (hypodermis) and intestine are major endocrine tissues, coordinating signals from the neurons about nutrients and conditions, and translating that information into decisions about longevity and reproduction. In our previous work, we found that reproductive aging and somatic aging rates are determined non-cell autonomously. However, the relevant tissues are relatively uncharacterized, due to the difficulty in isolating adult C. elegans tissues. My lab recently solved this problem, developing a method to gently dissociate adult C. elegans tissues, allowing us to sort cells and perform RNA-seq to identify the transcriptome of each tissue type in the animal. In this project, we will use our technique to obtain tissue-specific transcriptome information for every tissue (the "tissueome") and couple that information with computational approaches to identify networks of activity and communication. We will also use biochemical methods to determine tissue-specific transcription factor activity, which will allow us to understand how C. elegans integrates signals to convey metabolic and longevity decisions to the whole animal. C. elegans' small number of cells and simple tissues make it an ideal system in which to not only