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

Princeton University, Princeton NJ

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Abstract

? 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