The Changing Mouse Embryo Transcriptome at Whole Tissue and Single-Cell Resolution

Mammalian histogenesis is a sophisticated process of coordinated changes of cellular composition governed by selective gene expression. This thesis focuses on the systematic application of modern RNA-seq methods to histogenesis processes in developing mouse embryos. Most of the work presented here is conducted as part of the ENCODE (ENCyclopedia Of DNA Elements) Project. Chapter 1 introduces the current advances of transcriptome studies on tissue development. Chapter 2 discusses a large-scale study on the whole-tissue transcriptome of 12 embryonic tissues at up to 8 time points and 5 additional perinatal tissues. Coherent themes of biological function and underlying regulatory mechanisms are revealed from the large-scale analysis. Chapter 3 presents a high-resolution single-cell RNAseq study focused on the developing forelimb of the mouse embryo. This approach enables the assignment of differential genes to corresponding lineages and provides an even more accurate picture of RNA level patterns and regulatory modes. Finally, whole-tissue and single-cell methods are compared, contrasted, and integrated in Chapter 4 to extrapolate from the main discoveries of this thesis.