Student Theses and Dissertations

Date of Award

2014

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Fuchs Laboratory

Abstract

Tissue stem cells perform important functions throughout an organism’s life. They generate new cells to replenish cells that are lost during normal wear and tear or in response to acute injury. Remarkably, hair follicles naturally undergo repetitive cycles of regeneration and degeneration, a process that is accomplished with the support of stem cells within the hair follicles. It is this feature that makes this miniorgan an attractive model system to study stem cell biology. Interestingly, hair follicle is home to two distinct stem cell populations: epithelial hair follicle stem cells (HFSCs), which contribute to the formation of hair shafts, and melanocyte stem cells (McSCs), which contribute to hair pigmentation. During the hair cycle, HFSCs and McSCs work in harmony to generate a pigmented hair. However, little is known about the inter-stem-cell crosstalk governing this intricate coordination. To identify candidate transcription factors that specify HFSCs in mouse, the gene expression profiles of the HFSCs residing in the bulge of hair follicles versus the epithelial basal cells outside the bulge were compared. One of the “molecular signature” genes being upregulated in the HFSCs is nuclear factor I/B (Nfib). Embryonic ablation of Nfib revealed that Nfib is required for the hair follicle morphogenesis and hair folliclemediated re-epithelization during wound repair. Meanwhile, to address the function of Nfib in established HFSCs, I conditionally induced Nfib ablation in the adult HFSCs. Interestingly, I found that the ablation of Nfib in the adult HFSCs did not perturb the HFSC maintenance, as the growth of hair follicles and the hair cycle proceeded relatively normally. Instead, and even more unexpected, NFIB loss in the HFSCs promoted the proliferation and precocious differentiation of their nearby McSCs. These findings provide new insights into how McSC and HFSC behaviors maintain reliance upon cooperative factors within the hair follicle and how this might be uncoupled in injury, stress and disease states.

Comments

A Thesis Presented to the Faculty of The Rockefeller University in Partial Fulfillment of the Requirements for the degree of Doctor of Philosophy

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