Date of Completion

8-6-2013

Embargo Period

8-6-2013

Keywords

presomitic mesoderm, stem cell, niche, progenitor, single-cell analysis

Major Advisor

Craig E. Nelson

Associate Advisor

David J. Goldhamer

Associate Advisor

Andrew J. Pask

Associate Advisor

Charles Giardina

Field of Study

Genetics and Genomics

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

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.

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