Human epithelial stem cells are an invaluable resource for tissue regeneration, yet in spite of their clinical success we still are
seeking a clear understanding of the mechanisms that regulate their self-renewal and regenerative potential.
As it has been shown that translational regulation of self-renewal and differentiation plays a major role in adult epidermis, our goal is
to determine how ribosomal and epitranscriptomics mechanisms regulate gene expression to sustain the in vitro expansion and
commitment of epithelial stem cells.
Our single cell transcriptomic signatures of epithelial stem cells indicate a prominent role for genes regulating the epitranscriptome
and we hypothesize that changes in the committed state correspond to the activation of stage-specific translational and
epitranscriptomics signatures.
Therefore, we will use a combination of established genetic models and approaches for profiling ribosomal dynamics and tRNA
modifications to study the translational mechanisms taking place in cultured human epithelial stem cells. Our specific objectives are:
i) defining the translational dynamics and ii) determining the tRNA modification signature of epithelial stem and progenitor cells.
By testing our hypothesis at clonal level, we will define the key regulatory players and the mechanisms that influence the
progression along the differentiation route. This knowledge will potentially lead to a better identification of epithelial stem cells in
culture and could be harnessed to foster clinical applications in regenerative medicine.