Date of Completion
presomitic mesoderm, stem cell, niche, progenitor, single-cell analysis
Craig E. Nelson
David J. Goldhamer
Andrew J. Pask
Field of Study
Genetics and Genomics
Doctor of Philosophy
Experimental embryology and molecular genetic approaches have determined the murine presomitic mesoderm is derived from a long-lived progenitor located at the junction of the node and the regressing primitive streak. However, the precise identity of this presomitic mesoderm progenitor, i.e. its expression profile, and the molecular genetics of its niche, remain almost completely unknown. Understanding the complexities of the presomitic mesoderm progenitor, will provide great insight into the production of vertebrate presomitic mesoderm and its dervatives: muscle, bone, and cartilage.
This thesis describes the development of a robust quantitative and qualitative method for single cell transcriptional analysis followed by a novel use of the method to yield the first single cell deconstruction of an in vivo progenitor niche as applied to the identification of the presomitic mesoderm progenitor. My results yield a proposed transcriptional phenotype for the PMP and embed the phenotype within a genetic regulatory network model for its existence and maintenance. This lays the foundation for future work to test the functional characteristics of the phenotype and unravel the intricacies of its niche. Furthermore, this research highlights the important value of single cell analysis to identify distinct and often cryptic cell types in the complex heterogeneous environment of the developing embryo.
Jakuba, Caroline M., "Deconstruction of the Presomitic Mesoderm Progenitor Niche through Single-cell Analysis" (2013). Doctoral Dissertations. 145.