Smell You Later: Establishing and Activating Reserve, Dormant Stem Cells in the Olfactory Epithelium.
Abstract: Adult stem cells are characterized by the ability to differentiate into various cell lineages, while maintaining their own population. Characterization of these stem cells reveals that they can serve at least two, distinct functional roles throughout adult life. The first type of stem cell functions as an active, multipotent, progenitor cell that is nonetheless capable of long-term self-... read morerenewal. The second type of stem cell remains dormant, and rarely manifests a multipotent phenotype under normal conditions. Two stem cell populations, which support the dual-stem cell hypothesis presented above have been identified in the olfactory epithelium. Globose basal cell (GBC) act as the active population while horizontal basal cell (HBC) act as the dormant population. Here we demonstrate that the transcription factor p63 is a master regulator of HBC reserveness. We show that during the generation of HBCs, p63 is necessary and partially sufficient for the differentiation of other progenitors into HBCs. Conversely, p63 downregulation is necessary and sufficient for HBC activation. Finally, we show that HBCs can give rise to long lived stem cells other than themselves, indicating that there is a dynamic flux between active and reserve stem cells. Taken together, the findings identify a cell-autonomous transcriptional mechanism that regulates stem cell transitions, self-renewal and differentiation. Such a mechanism is likely to be relevant to our ability to utilize these populations therapeutically, as well as to our understanding of stem cell dynamics in general.
Thesis (Ph.D.)--Tufts University, 2014.
Submitted to the Dept. of Cell, Molecular & Developmental Biology.
Advisor: James Schwob.
Committee: Grace Gill, Victor Hatini, Charlotte Kuperwasser, and Satrajit Sinha.
Keywords: Cellular biology, Neurosciences, and Developmental biology.read less