Abstract
Tissue-specific gene expression plays a fundamental role in metazoan biology and is an important aspect of many complex diseases. Nevertheless, an organism-wide map of tissue-specific expression remains elusive due to difficulty in obtaining these data experimentally. Here, we leveraged existing whole-animal Caenorhabditis elegans microarray data representing diverse conditions and developmental stages to generate accurate predictions of tissue-specific gene expression and experimentally validated these predictions. These patterns of tissue-specific expression are more accurate than existing high-throughput experimental studies for nearly all tissues; they also complement existing experiments by addressing tissue-specific expression present at particular developmental stages and in small tissues. We used these predictions to address several experimentally challenging questions, including the identification of tissue-specific transcriptional motifs and the discovery of potential miRNA regulation specific to particular tissues. We also investigate the role of tissue context in gene function through tissue-specific functional interaction networks. To our knowledge, this is the first study producing high-accuracy predictions of tissue-specific expression and interactions for a metazoan organism based on whole-animal data.
Highlights
Tissue-specific gene expression is a fundamental aspect of multicellular biology, underlying the development, function, and maintenance of diverse cell types within an organism
Our results provide a global view of tissue-specific expression in Caenorhabditis elegans, allowing us to address the question of how expression patterns are regulated and to analyze how the functions of genes that are expressed in several tissues are influenced by the cellular context
Analysis of two developmental time courses [24] revealed dramatic tissue-specific temporal patterns that reflect developmental timing; as might be expected because neurons are born in early larval stages, earlier developmental stages are enriched for neuronal transcripts, while later stages are enriched for germ line transcripts, correlating with the development of reproductive tissues and the onset of reproduction (Figure 1B)
Summary
Tissue-specific gene expression is a fundamental aspect of multicellular biology, underlying the development, function, and maintenance of diverse cell types within an organism. Accounting for tissue-specific expression is a precursor to any systems-level understanding of metazoan organismal development and function and large-scale studies of spatio-temporal gene expression both at the single-gene and whole-genome level have been performed in several organisms [1,2,3,4,5]. Its invariant cell lineage allows single-cell resolution of tissue-specific expression patterns through a variety of experimental techniques [5,8]. Several methods have been developed to isolate mRNA samples enriched for a specific tissue or cell type, allowing global analysis using microarrays or SAGE [13,14,15,16,17,18,19,20,21,22]
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