UC San Diego

Every cell in the body arises from a single fertilized cell that, through many cell divisions and transitions from one type to another, travels a landscape of possible fate decisions during development. Though adult cell types have been well cataloged molecularly and functionally, the states a cell can pass through and the genes that regulate these choices remain unclear. Recent advances in quantitative cellular measurements for monitoring global gene regulation simultaneously in hundreds to thousands of single cells from an experiment is allowing for the discovery of cell types and cell states as well as the trajectories linking them. This dissertation is comprised of investigation of, and applies towards, the developmental states and genetic regulation of mouse mesoderm.

The goal of the first study was to catalog cell types and states during mouse mesodermal developmental by gene expression at the single cell level (Chapter 2). We determined developmental trajectories for six mesodermal cell types, providing putative novel cellular intermediates with previously undocumented gene expression profiles. The goal of the second study was to functionally investigate a cellular intermediate identified in the first study that had not been previously described.

These studies describe new findings concerning the cellular and molecular hierarchy of mesodermal development that will enable further study of genetic regulation of developing cell types. Mapping developmental landscapes may promote the discovery of genes and pathways that govern cell fate decisions and transitions essential for advancements in understanding the etiology of disease and the development of medical therapies.