"Regulation by Long Non-Coding RNAs in Epidermal Differentiation"
Host lab: Anthony Oro
Stanford University School of Medicine
Stem cell based therapies are a promising treatment option for patients who suffer from extensive burns or genetic skin diseases such as Dystrophic Epidermolysis Bullosa. Differentiating epidermal cells requires understanding of molecular signals, gene expression patterns and transcriptional regulatory networks involved in skin development. Developmental regulation is influenced by both coding and non-coding genes. Long non-coding RNAs (lncRNAs) resemble mRNA transcripts yet are not translated to proteins. It is expected that lncRNA transcripts coordinated with a network of transcription factors play an essential role in developmental regulation and lineage commitment from the stem cell state to stratified skin. The underlying mechanism of non-coding RNA regulation in skin commitment and development is unknown. Here we investigate differentially expressed lncRNAs and novel transcription factors and their role in differentiation and self-renewal in human keratinocytes, representing the latest stage of skin development. Transcriptome analysis revealed expression patterns from over 100 differentially expressed lncRNA targets in 4 stages of epidermal development. Loss of function studies indicate lncRNAs are necessary for proper keratinocyte viability, proliferation and self-renewal. In addition the lncRNA targets are essential for stratification determined by lift-up assays in organotypic cultures. Based on the current results it is anticipated that functional assays will define the molecular mechanisms of the lncRNA targets in epidermal stratification. Impending work will identify essential lncRNAs in early ectoderm and late epidermal differentiation that may improve stem cell based therapies for patient use.