- Main
The Role of microRNAs in Olfactory Regeneration
- Estrada, Jose Emilio
- Advisor(s): Ngai, John
Abstract
The mammalian main olfactory epithelium is the sensory tissue dedicated to detecting volatile chemical odorants that contribute to our social and natural environment. Natural neuronal turnover throughout adulthood and the ability to regenerate large amounts of damaged tissue are unique properties of the main olfactory epithelium in adult mammals. Independent stem cell populations are activated to give rise to two distinct modes of neurogenesis: transit amplifying globose basal cells maintain homeostatic neuronal turnover while horizontal basal cells enter the cell cycle and regenerate all cell types of the OE upon severe injury. Recent evidence has pointed toward the role of specific miRNAmRNA interactions in the regulation of stem cell self-renewal and differentiation
The ability to observe these two modes of adult neurogenesis in vivo,
homeostatic maintenance and regeneration after severe injury, makes the main
olfactory epithelium an excellent model in which to study the molecular regulation
of stem cells as they enter the cell cycle and differentiate into mature neuronal
progeny. However, to fully understand the mechanisms regulating these
processes it is imperative to elucidate both the nature and extent of these
interactions at the genome-wide level. Our work in profiling the horizontal basal
cell transcriptome provides supporting evidence that a large portion of the
transcriptome may be regulated by miRNA mediated repression, which acts by
reinforcing an undifferentiated state. Genetic ablation of miRNA biogenesis
machinery shows that miRNA are necessary to repress aberrant cell cycle reentry
and may promote the expression of the stem cell maintenance gene
Transforming protein 63.
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