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The Role of microRNAs in Olfactory Regeneration

  • Author(s): Estrada, Jose Emilio
  • Advisor(s): Ngai, John
  • et al.
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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