MicroRNAs as Markers of Developmental Competency Towards Insulin Producing Cells
My lab studies molecular regulation of stem cell differentiation into insulin producing cells (beta cells). Different stem cell lines are clearly distinct in their capacity to develop specifically into beta cells. For stem cells to be clinically useful for the treatment of diabetes, efficient methods are necessary to identify genetic markers of beta cell competent cell lines. We hypothesize that a relevant diagnostic fingerprint can be elucidated in early differentiation by analyzing small RNA expression.
MicroRNAs (miRNAs), small RNAs that bind protein coding genes, can regulate hundreds of genes within a cell, and the threshold level of miRNA expression within certain cells can determine cell fate decisions. Therefore they are excellent candidates for genetic markers, and tools for manipulating stem cell differentiation in vitro. Furthermore, because miRNAs are small molecules, they can be introduced into cells without genetic modification of the cell. Thus, they are ideal as safe reagents for stem cell therapies.
We plan to compare different stem cell lines in their ability to produce beta cells in vitro. We will then correlate miRNA expression between cell lines to identify diagnostic markers that can be used for efficient monitoring of stability and beta cell competence of cells generated for clinical use. In addition, candidate miRNAs will be manipulated in order to test their ability to improve differentiation towards the beta cell lineage. These combined goals should lead to improved methods for creating beta cells in vitro, as well as identification of cell lines suitable for cell replacements therapies.